Efficacy and Safety of Ciprofloxacin Treatment in Urinary Tract Infections (Utis) in Adults: a Systematic Review with Meta-Analysis
Gaceta Médica de México. 2015;151
Contents available at PubMed www.anmm.org.mx PERMANYER Gac Med Mex. 2015;151:210-28 www.permanyer.com
GACETA MÉDICA DE MÉXICO REVIEW ARTICLE
Efficacy and safety of ciprofloxacin treatment in urinary tract infections (UTIs) in adults: a systematic review with meta-analysis
1 2 2 2
Pedro Gutiérrez-Castrellón *, Luisa Díaz-García , Agustín de Colsa-Ranero , Juan Cuevas-Alpuche © Permanyer Publications 2015
.rehsilbup eht fo noissimrep nettirw roirp eht tuohtiw gniypocotohp ro decudorper eb yam noitacilbup siht fo trap oN trap fo siht noitacilbup yam eb decudorper ro and Irma Jiménez-Escobargniypocotohp 1 tuohtiw eht roirp nettirw noissimrep fo eht .rehsilbup 1Hospital General Dr. Manuel Gea González, México, D.F.; 2Instituto Nacional de Pediatría, Secretaría de Salud, México, D.F., México
Abstract
Objectives and Design: A systematic review with meta-analysis of randomized controlled trials (RCT) on the efficacy and safety of ciprofloxacin in the treatment of acute or complicated urinary tract infections in adults. Primary outcomes were bacteriological eradication, clinical cure, bacterial resistance, and adverse event rates. Results: Initially, 111 RCTs were identified. We excluded 81 studies due to low quality methodology. An analysis of the remaining RCTs identified therapeutic equivalence of ciprofloxacin against other antimicrobials in terms of bacterial eradication and clinical cure at the end of treatment and in subsequent stages. The percentage of bacterial resistance was similar in both groups, while the percentage of related adverse events was significantly lower in the groups treated with ciprofloxacin. Conclusions: We conclude that ciprofloxacin is a safe and effective therapeutic alternative for the treatment of acute or complicated urinary tract infections in adults. (Gac Med Mex. 2015;151:210-28) Corresponding author: Pedro Gutiérrez-Castrellón, [email protected]
KEY WORDS: Ciprofloxacin. Urinary tract infection. Adult.
treatments and the length of urinary tract functionality and ntroduction I integrity assessment2-4. Organisms more commonly re- sponsible for UTIs are gram-negative bacteria of the En- Urinary tract infections (UTIs) (upper urinary pathogen- terobacteriaceae group; Escherichia coli is responsible ic bacteria levels higher than 100,000 colony-forming for 80% of UTIs, followed by Staphilococcus saprophyti- units per urine ml [CFU/ml], with or without associated cus, particularly in young women5. From the therapeutic symptoms) are one of the most common infectious dis- point of view, one of the first meta-analysis intended to eases in all age groups and are among the medical assess the effectiveness of antimicrobial treatment for conditions that most frequently require outpatient man- UTIs in patients younger than 65 years of age was pub- agement. A global annual incidence of 250 million cases lished in 2004. The use of antibiotics during the active has been estimated, with significant direct and indirect phase of treatment was shown to significantly reduce the costs1. The distinction between complicated and uncom- risk of bacterial recurrence by 79% (risk ratio [RR]: 0.21 plicated UTI is highly important due to implications relat- [0.13-0.34]; p = 0.00001) and the risk of clinical recur- ed, among other aspects, to pre- and post-treatment rence by 85% (RR: 0.15 [0.08-0.28]; p = 0.00001), without assessment, type and duration of selected antimicrobial significant differences between groups being observed
Correspondence: *Pedro Gutiérrez-Castrellón Hospital General Dr. Manuel Gea González Calzada de Tlalpan, 4800 Col. Sector XVI, Del. Tlalpan, C.P. 14080, México, D.F., México E-mail: [email protected] Date of modified version reception: 12-01-2014 Date of acceptance: 03-07-2014 210 P. Gutiérrez-Castrellón, et al.: Ciprofloxacin and urinary tract infections in adults after treatment conclusion. With regard to adverse events, quinolones (including fluoroquinolones) and fosfomycin, the antibiotic-treated group had 58% more serious ad- although the increase in co-trimoxazole resistance has verse events, although the difference between groups reduced its therapeutic efficacy and, consequently, its was not significant (RR: 1.6 [0.47-5.3]; p = non-significant use14-17. Since 1977, quinolones have become the cor- [NS])6. A second systematic review was published in nerstone of treatment for different serious bacterial infec- 2005, where optimal duration of antimicrobial therapy for tions. These are nalidixic acid-related antibacterial struc- the treatment of IVUs in non-pregnant woman from 18 to tures, with excellent bioavailability, adequate tissue 65 years of age was assessed; 33 randomized controlled penetration and relatively reduced presence of adverse trials (RCTs) were included, with a total of 9,605 women. events. They have been used mainly in the treatment of The short (3 days) was compared with the long treatment UTIs and prostatitis, although there is also evidence of regimen (5 to 10 days). Overall, short-term failure was no their use in enteral bacterial infections, biliary tree infec- different between both groups (RR: 1.06 [0.88-1.28]; p = tions, sexually transmitted diseases and neutropenic im- © Permanyer Publications 2015 .rehsilbup eht fo noissimrep nettirw roirp eht tuohtiw gniypocotohp ro decudorper eb yam noitacilbup siht fo trap oN trap fo siht noitacilbup yam eb decudorper ro 0.52), and nogniypocotohp differences weretuohtiw observedeht when trialsroirp us- munosuppressednettirw host prophylaxis.noissimrep fo Of all eht quinolones, the .rehsilbup ing the same antibiotics in both arms (RR: 1.15 [0.95- most succesful and most widely used compound is with 1.39]; p = NS) and those using different antibiotics (RR: no doubt ciprofloxacin, which was patented in 1983 and 0.90 [0.62-1.29]; p = NS] were separately analyzed7. A approved for use in the USA by the Food and Drug Ad- third systematic review comparing different antibiotic ministration (FDA) in 1987. With regard to the use of cip- routes of administration was published in 2007; 15 RCTs rofloxacin for the management of UTIs, a significant num- with different types of antimicrobials and treatment dura- ber of RCTs have been conducted assessing the safety, tions, most of them conducted in non-pregnant women, efficacy and tolerability of this quinolone since 198623,127, were included. The rates of clinical cure and reinfection but no systematic review with meta-analysis thoroughly were shown not to be significantly different between assessing its efficacy and safety in the treatment of UTIs groups (RR: 1.01 [0.94-1.1] and RR: 0.76 [0.30-1.90]) with in adults has been published to this moment. the use of “switch” therapy with initial intramuscular (IM) or intravenous (IV) administration followed by oral admin- Methods istration versus continuous IM or IV therapy8. With regard to theatment in subjects older than 65 years or in popu- All published RCTs that had compared, in one of their lations in special situations, two systematic reviews were treatment arms, ciprofloxacin against other antimicrobi- identified as far as December 2009. The first was pub- al in patients older than 18 years of age with positive lished in 2002 and included 15 RCTs with a total of 1,644 urine culture (> 105 UFC/ml) regardless of the presence patients; it concluded that persistent UTI was less per- of acute cystitis (dysuria, urinary urgency, urinary fre- sistent in patients who received treatment for 3-6 days quency or suprapubic pain), allowing to clearly identify (RR: 2.01 [1.05-3.54]: p = 0.03), although this effect was the presence or not of risk factors for the development not maintained after 2 weeks’ follow-up (RR: 1.18 [0.59- of UTIs (indwelling or intermittent urinary catheters, ob- 2.3]. Patients treated with short regimens (< 7 days) structive uropathy, vesicoureteral reflux and other uro- showed higher risk of persistent UTI in the 2-week fol- logical abnormalities) were selected, which later gave low-up (RR: 1.93 [1.01-3.7]; p = 0.047), although not in the us opportunity to perform stratified analyses in patients long-term (RR: 1.28 [0.89-1.84])10. The second review, with acute UTIs (non-complicated) or UTIs in patients without a meta-analysis, published in 2006 and conducted with risk factors; additionally, efficacy, safety or tolera- in extended care facilities residents, concluded that anti- bility of ciprofloxacin should have been clearly reported, biotics were useful in reducing the rate of UTIs in these regardless of the dose, route of administration and treat- patients9. Currently known factors that have to be consid- ment duration. Bacteriological erradication at the end of ered for the selection of UTI treatments include the agent’s treatment, persistence of bacterial erradication the days antimicrobial activity (broad or reduced), pharmacokinetic after treatment termination, presence of clinical cure the characteristics that enable their use for longer intervals, days after treatment termination, the rate of bacterial prevalence of uropathogens local resistence, antimicro- resistances and the frequency of related adverse events bial urinary levels optimal duration, effect on fecal and were considered the outcome measures. Two of the vaginal flora, the potential for the development of unfa- authors of this review independently identified articles vorable side-effects and treatment costs11-13. Antimicro- published in English and Spanish. The consulted data- bials with proven efficacy in the management of UTIs bases were: The Cochrane Central Register of Con- include co-trimoxazole (trimethoprim/sulfamethoxazole), trolled Trials (CENTRAL) at The Cocharane Linrary; 211 Gaceta Médica de México. 2015;151
Medline, using the highly sensitive search strategy de- disregarded in the first evaluation for the reasons de- veloped by The Cocharane Collaboration for RCTs iden- scribed in table 1 and 30 articles were selected for tification130, and Embase, using the search strategy further analysis and for the development of the me- adapted by The Cochrane Collaboration for the search ta-analysis20-130 (Tables 2, 3, 4 and 5). The analysis of of RCTs in this database131. Specific MeSH descriptors relevant evidence allowed for therapeutical evidence used in this search were the following: (urinary tract of ciprofloxacin equivalence with the other antibiotics infections[MH] OR UTI*[TIAB] OPR acute cystitis[TIAB] used as comparators to be identified in terms of becte- OR cystitis[MH] OR Escherichia coli Infections[MH] riological erradication and clinical cure at the end of AND Quinolone[MH] OR Anti-Infective Agents, Uri- treatment (RR: 1.01 [0.99-1.03]; p = NS and RR: 0.99 nary[MH] OR Quinolon*[TIAB] OR Fluoroquinolon*[TIAB] [0.98-1.01]; p = NS, respectively), as well as in bacteri- OR (ciprofloxacin OR norfloxacin OR lomefloxacin OR ological erradication and clinical cure maintenance in
levofloxacin OR ofloxacin OR pefloxacin OR rufloxacin stages following treatment finalization (RR: 1.03 [1.0- © Permanyer Publications 2015 .rehsilbup eht fo noissimrep nettirw roirp eht tuohtiw gniypocotohp ro decudorper eb yam noitacilbup siht fo trap oN trap fo siht noitacilbup yam eb decudorper ro OR moxifloxacingniypocotohp OR gatifloxacintuohtiw OReht sparfloxacinroirp OR 1.07];nettirw p = 0.06 and RR: 0.99-1.0];noissimrep fo p = NS,eht respectively). .rehsilbup fleroxacin OR enoxacin OR Nalidixic Acid)[TIAB]). Ad- The percentage of bacterial resistances was also similar ditionally, a search for evidence was performed in Lilacs in both groups (RR: 1.01 [0.80-1.27]; p = NS), while the (from 1980 to 2010), in Artemisa (from 1999 to 2005) percentage of observed adverse events was significant- and in grey literature obtained through manual search ly lower in the groups of patients treated with ciproflox- or enquiry via e-mail. Evidence review was conducted acin (RR: 0.82 [0.75-0.91]; p = 0.0001) (Figs. 1 to 6). in a blinded and independent fashion by three authors When the analysis of identified evidence in cases of of this review who, after carefully analyzing each article, UTIs in subjects with risk factors was conducted, ther- disregarded those considered not relevant for the pur- apeutic equivalence was observed between ciprofloxa- poses of the review. In case of disagreements between cin and the rest of antibiotics used as comparators with reviewers, agreement was reached by applying the pan- regard to bacteriological erradication and clinical cure el of the Delphi method. Allocation schemes were clas- at the end of treatment (RR: 1.0 [0.96-1.04]; p = NS and sified as adequate (randomization methods that didn’t RR: 0.98 [0.96-1.01]; p = NS, respectively), as well as allow for the investigator or the patient to know or influ- with bacteriological erradication and clinical cure main- ence on patient allocation), unclear (not sufficient infor- tenance in stages subsequent to treatment finalization mation available to reach a judgement) or inadequate (RR: 1.0 [0.94-1.05]; p = NS and RR: 0.97 [0.93-1.02]; (description of randomization methods as non-opaque p = NS, respectively). The percentage of bacterial re- envelopes or presence of information allowing for a bi- sistances was also similar between groups (RR: 1.06 ased assignment of the study subject to some group in [0.78-1.4]; p = NS), whereas the percentage of ob- particular). Statistical analysis of the results was con- served adverse events was significantly lower in the ducted using the STATA 11.0 statistical package for groups of patients treated with ciprofloxacin (RR: 0.8 Mac, considering the sub-routines for the development [0.67-0.96]; p = 0.01) (Figs. 7 to 12). When the analysis of meta-analyses. For dichotomous outcomes (e.g., of evidence identified in acute UTIs cases (non-compli- bacteriological erradication vs. no erradication), the re- cated) was performed, therapeutic equivalence was sults were expressed as the RR with a 95% confidence observed between ciprofloxacin and the other antibiot- interval (95% CI), whereas for continuous measuring ics used as comparators with regard to bacteriological scales, data were expressed through the weighted erradication and clinical cure by the end of treatment mean difference (WMD). In the cases where primary (RR: 1.01 [0.99-1.04]; p = NS and RR: 1.0 [0.98-1.02]; exploration allowed for a heterogeneity value (I2) higher p = NS, respectively). A discrete therapeutic superiority than 60% to be identified, the decision was made to of ciprofloxacin was observed in the maintenance of analyze the results using a random effects model (in- bacteriological erradication in stages subsequent to verse of the variance). Statistical heterogeneity was ex- treatment finalization (RR: 1.08 [1.01-1.16]; p = 0.01), plored using Egger’s graphs, and publication bias was whereas clinical cure maintenance was similar between assessed using a funnel plot. groups (RR: 0.99 [0.97-1.02]; p = NS). The percentage of bacterial resistances was similar between groups Results (RR: 0.97 [0.67-1.3]; p = NS), whereas the percentage of observed adverse events was significantly lower in the One-hundred and eleven randomized controlled trials groups op patients treated with ciprofloxacin (RR: 0.88 were identified and entirely reviewed; 81 articles were [0.81-0.96]; p = 0.003) (Figs. 13 to 18). 212 P. Gutiérrez-Castrellón, et al.: Ciprofloxacin and urinary tract infections in adults
Table 1. Description of excluded trials
Authors Reason for exclusion
Giamarellou rt al.129 Experience with ciprofloxacin in vitro
Gonzalez et al.128, McCue et al.81, Rao et al.71 Ciprofloxacin pharmacokinetics in healthy volunteers
Garlando et al.126, Raz et al.112, Karachalios et Comparison of different doses of ciprofloxacin al.107
Kosmidis et al.123 Fleroxacin in UTI with no comparator
Shearman et al.122, Hall et al.77, Lukkarinen et al.72 Ciprofloxacin in prostatectomy prophylaxis
Cox 113 Ciprofloxacin in transurethral surgery prophylaxis © Permanyer Publications 2015 120 118 119
.rehsilbup eht fo noissimrep nettirw roirp eht tuohtiw gniypocotohp ro decudorper eb yam noitacilbup siht fo trap oN trap fo siht noitacilbup yam eb decudorper ro Fass et al.gniypocotohp , Gallis et al. , Levinetuohtiw et al.eht , roirp Ciprofloxacin vs. ceftazidimenettirw for the tratmentnoissimrep of non-urinaryfo seriouseht .rehsilbup Peacock et al.117, Quintero-Perez et al.115, infections Sifuentes-Osornio et al.114, Villavicencio et al.116, Paladino et al.103
Boyko et al.109 Amoxicillin vs. TMP in UTIs
Brouwer et al.108 Ciprofloxacin in vaginal hysterectomy
Van Poppel et al.111 Ciprofloxacin in transurethral maneuvers prophylaxis
Wolfhagen et al.110 Fleroxacin at 200 or 400
Iravani102 Efficacy of the use of temafloxacin
Lew et al.105 Ciprofloxacin for infection prophylaxis in subjects undergoing bone marrow transplantation
Bailey et al.99 Ciprofloxacin in pyelonephritis
Hibberd et al.95 TMP vs. ciprofloxacin in renal transplantation prophylaxis
Kalager et al.101 Ciprofloxacin vs. tobramycin + cefuroxime in serious infections
Vander der Wall et al.97 Prophylaxis for urinary catheter-associated infections
Childs90, Pittman et al.91, Pummer89 Fleroxacin vs. norfloxacin in complicated or uncomplicated UTIs
Cox87 Fleroxacin vs ceftazidime
Naber et al.88 Fleroxacin vs. ofloxacin in complicated UTIs
Whitby et al.85 Fleroxacin vs. amoxicillin
Biering-Sorensen et al.84 UTI prophylaxis in bone marrow injuries
Darouiche et al.82 Urodynamic studies prophylaxis
Pfau et al.83 Post-coital quinolone prophylaxis in recurrent UTIs
Gasser et al.75 Fleroxacin in transurethral surgery
Bierkens et al.73 Prophylaxis in lithotripsy
Lukkarinen et al.79 Antibiotic prophylaxis in transurethral prostatectomy
Moyses Neto et al.69 Prophylaxis in renal transplantation
Hsieh et al.67 Ciprofloxacin in cirrhosis
Kapoor et al.65 Prophylaxis in transrectal biopsy
Naber et al.66 Bactericidal activity of fleroxacin and pefloxacin in healthy volunteers
Tsugawa et al.64 Prophylaxis in urethrocystoscopy
Viitanen et al.68 Fleroxacin in transuterhral prostatectomy
Eickhoff et al.58 Ciprofloxacin in epididymitis
Continues
213 Gaceta Médica de México. 2015;151
Table 1. Description of excluded trials (continued)
Authors Reasons for exclusion
Mombelli et al.63 Oral ciprofloxacin vs. IV ciproploxacin for pyelonephritis
Naber et al.56 IV ciprofloxacin vs. oral ciprofloxacin bactericidal activity
Price et al.57 Assessment of CPGs in the mangement of infections in SICUs
Tsukamoto et al.60 Ciprofloxacin vs. ciprofloxacin + macrolide
Aron et al.54 Prophylaxis in prostate biopsy
Christiano et al.55 Prophylaxis in endourologic surgery
Henry et al.59 Use of ciprofloxacin OD or BID © Permanyer Publications 2015 .rehsilbup eht fo noissimrep nettirw roirp eht tuohtiw gniypocotohp ro decudorper eb yam noitacilbup siht fo trap oN trap fo siht noitacilbup yam eb decudorper ro gniypocotohp tuohtiw eht roirp nettirw noissimrep fo eht .rehsilbup Naber et al.48 Lomefloxacin vs. ciprofloxacin for prostatitis
Richard et al.51 Single dose vs. three + quinolones
Ulleryd et al.46 Use of ciprofloxacin from 2 to 4 weeks
Wagenlehner et al.45 Bactericidal activity in healthy volunteers
Dow et al.37 3 vs. 14-day treatment in UTI in bifid spine
Sabbagh et al.39 3 vs. 7-day prophylaxis in transrectal biopsy
Talan et al.44 Extended-release formulation every 24 h vs. twice daily
Valdevenito et al.41 Prophilaxis in prostate transurethral resection
Vogel et al.43 3 vs. 7 days
Wazait et al.36 UTI risk reduction after catheter removal
Wells et al.40 Ertapenem vs. ceftriaxone
Gupta et al.34 Treatment of resistant E. coli after prostatectomy
Bin et al.31 Comparison of ceftazidime, impinemem and cefoperazone
Esposito et al.28 Prevention of catheter-associated infections
Kartal et al.32 Prevention of bacteriuria after urodynamic study
Mariappan et al.30 Prevention of post-nephrolithotomy UTI
Wagenlehner et al.45 Pharmacokinetics in healthy volunteers
Wagenlehner et al.33 Bioavailability in healthy volunteers
Marcelin-Jimenez et al.27 Bioavailability and phenazopyridine
Peterson et al.25 Pre-treatment identification and susceptibility
Cam et al.21 Infection prevention in transrectal biopsy
Dybowski et al.24 Microbiology in acute cystitis
Tuncel et al.22 Post-prostatic biopsy complications reduction
Mirone et al.19 Comparison of ciprofloxacin extended vs. immediate release
Pfefferkorn et al.20 Infection prevention at urinary catheter removal
214 P. Gutiérrez-Castrellón, et al.: Ciprofloxacin and urinary tract infections in adults
Table 2. Characteristics of studies included in the meta-analysis (acute UTI)
Author Year Treatment 1 Treatment 2 n1 n2 Multi-center Blinding Randomized
Naber et al.38 2004 Ciprofloxacin Gatifloxacin 400 mg SD 360 371 Yes Double Yes 500 mg BID x 5 days
Naber et al.38 2004 Ciprofloxacin Gatifloxacin 300 mg BID 360 371 Yes Double Yes 500 mg BID x 3 days x 5 days
Auqer et al.50 2002 Ciprofloxacin Norfloxacin 400 mg BID 164 161 Yes Double Yes 500 mg SD x 3 days
52 Gomolin et al. 2001 Ciprofloxacin TMP 160/800 mg BID 86 86 Yes Oben label Yes © Permanyer Publications 2015
.rehsilbup eht fo noissimrep nettirw roirp eht tuohtiw gniypocotohp ro decudorper eb yam noitacilbup siht fo trap oN trap fo siht noitacilbup yam eb decudorper ro gniypocotohp 250 tuohtiw mg BID eht x 10 days roirp nettirw noissimrep fo eht .rehsilbup x 10 days
Iravani et al.61 1999 Ciprofloxacin TMP 160/800 mg BID 168 174 Yes Double Yes 100 mg BID x 7 days x 3 days
Iravani et al.61 1999 Ciprofloxacin Nitrofurantoin 100 mg 168 179 Yes Double Yes 100 mg BID BID x 7 days x 3 days
Henry et al.59 1999 Ciprofloxacin Sparflox 400 mg SD 386 395 Yes Double Yes 250 mg BID x 7 days
Henry et al.59 1999 Ciprofloxacin Sparflox 200 mg OD 386 394 Yes Double Yes 250 mg BID x 3 days x 7 days
McCarty et al.62 1999 Ciprofloxacin Ofloxa 200 mg BID 229 228 Yes Double Yes 100 mg BID x 3 days x 3 days
McCarty et al.62 1999 Ciprofloxacin TMP 160/800 mg BID 229 231 Yes Double Yes 100 mg BID x 3 days x 3 days
Iravani et al.80 1996 Ciprofloxacin Norfloxacin 400 mg BID 249 227 Yes Double Yes 500 mg BID x 5 days x 5 days
Iravani et al.86 1993 Ciprofloxacin Fleroxacin 200 mg OD 204 180 Yes Double Yes 250 mg BID x 7 days x 7 days
Pfau et al.92 1993 Ciprofloxacin Ofloxacin 400 mg SD 59 59 No Double Yes 500 mg SD
Pfau et al.92 1993 Ciprofloxacin Norfloxacin 800 mg SD 58 57 No Double Yes 500 mg SD
Henry et al.128 1986 Ciprofloxacin TMP/SMX 160/800 mg 31 34 No Double Yes 250 mg BID TID x 10 days x 10 days
NR: not reported
215 Gaceta Médica de México. 2015;151 NR NR NR NR NR NR NR (%) 0.04 0.05 0.13 0.06 0.13 0.07 0.03 0.04 Bact. Bact. resist. resist. Control Control NR NR NR NR NR NR NR 0.05 0.05 0.04 0.12 0.12 1.04 0.04 0.05 with with Bacterial Bacterial end of treatment treatment of end resistance at the the at resistance ciprofloxacin (%) (%) ciprofloxacin © Permanyer Publications 2015 NR NR NR NR .rehsilbup eht fo noissimrep nettirw roirp eht tuohtiw gniypocotohp ro decudorper eb yam noitacilbup siht fo trap oN trap fo siht noitacilbup yam eb decudorper ro gniypocotohp tuohtiw eht roirp nettirw noissimrep fo eht .rehsilbup (%) 0.82 0.88 0.95 0.88 0.95 0.93 0.79 0.81 0.91 0.89 0.95 Post- Post- Control Control Clin. cure cure Clin. NR NR NR NR 0.86 0.86 0.91 0.97 0.90 0.90 0.81 0.81 0.91 0.91 0.89 with with clinical cure cure clinical after treatment treatment after Maintenance of of Maintenance ciprofoxacin (%) ciprofoxacin NR NR NR NR NR (%) 0.45 0.46 0.78 0.82 0.81 0.89 0.84 0.87 0.90 0.89 Post- Control Control Bact. err. err. Bact. NR NR NR NR NR 0.48 0.48 0.91 0.91 0.92 0.92 0.89 0.89 0.80 0.93 with with erradication erradication after treatment treatment after Maintenance of of Maintenance ciprofoxacin (%) ciprofoxacin NR NR NR (%) End End 0.81 0.85 0.71 0.85 0.95 0.93 0.93 0.90 0.95 0.96 0.97 0.97 Control Control Clin. cure cure Clin. NR NR NR (%) 0.84 0.84 0.75 0.97 0.95 0.95 0.89 0.89 0.93 0.93 0.97 0.98 Clinical cure cure Clinical at the end of of end the at ciprofloxacin ciprofloxacin treatment with with treatment (%) 0.48 0.56 0.92 1.84 0.93 0.77 0.93 0.92 0.93 0.97 0.94 0.96 0.97 0.88 0.94 Bact. Bact. Control Control err. End err. 0.49 0.49 0.91 0.93 0.88 0.88 0.97 0.97 0.94 0.94 0.90 0.89 0.97 0.97 1.00 the end of of end the treatment with with treatment erradication at at erradication Bacteriological Bacteriological ciprofloxacin (%) ciprofloxacin 62 62 52 61 61 80 38 38 50 59 59 127 92 92 86 Pfau et al. et Pfau et al. Henry Naber et al. Naber Naber et al. Naber et al. Auqer al. et Gomolin al. et Iravani al. et Iravani et al. Henry et al. Henry al. et McCarty al. et McCarty al. et Iravani Iravani al. et Pfau Authors Authors NR: not reported not NR: Table 3. Characteristics of the studies included in the meta-analysis (acute UTI) (acute meta-analysis the in included studies the of Characteristics 3. Table
216 P. Gutiérrez-Castrellón, et al.: Ciprofloxacin and urinary tract infections in adults
Table 4. Characteristics of studies included in the meta-analysis (complicated UTI)
Author Year Treatment 1 Treatment 2 n1 n2 Multi-center Blinding Randomized
Peterson et al.23 2008 Ciprofloxacin Levofloxacin 391 391 Yes Double Yes 400 mg BID 750 mg OD x 5 days x 10 days Klausner et al.26 2007 Ciprofloxacin Levofloxacin 165 146 Yes Double Yes 400 mg BID 750 mg OD x 5 days x 3 days Carmignani et al.35 2005 Ciprofloxacin Prulifloxacin 130 127 Yes Double Yes 500 mg BID 600 mg OD x 5 days x 10 days Naber et al.42 2004 Ciprofloxacin Gatifloxacin 188 189 Yes Double Yes 500 mg BID 400 mg SD © Permanyer Publications 2015 .rehsilbup eht fo noissimrep nettirw roirp eht tuohtiw gniypocotohp ro decudorper eb yam noitacilbup siht fo trap oN trap fo siht noitacilbup yam eb decudorper ro gniypocotohp tuohtiw eht roirp nettirw noissimrep fo eht .rehsilbup x 5 days Naber et al.42 2004 Ciprofloxacin Gatifloxacin 188 181 Yes Double Yes 500 mg BID 300 mg BID x 5 days x 3 days Cox et al.49 2002 Ciprofloxacin Gatifloxacin 183 189 Yes Double Yes 500 mg BID 400 mg OD x 5-7 days x 5-7 days Raz et al.53 2000 Ciprofloxacin Ofloxacin 200 214 213 Yes Double Yes 250 mg BID mg BID x 7 days x 7 days Frankenschmidt et al.70 1997 Ciprofloxacin Fleroxacin 67 66 Yes Open label Yes 250 mg BID 200 mg OD x 7 days x 7 days Frankenschmidt et al.70 1997 Ciprofloxacin Fleroxacin 103 108 Yes Open label Yes 500 mg BID 400 mg OD x 7 days x 7 days Naber et al.78 1996 Ciprofloxacin Sparfloxacin 264 252 Yes Double Yes 500 mg BID 100 mg OD x 10 days x 10 days Whitby et al.74 1996 Ciprofloxacin Fleroxacin 65 68 No Double Yes 500 mg BID 400 mg OD x 10 days x 10 days Schaeffer et al.94 1992 Ciprofloxacin Norfloxacin 35 37 No Open label Yes 500 mg BID 400 mg BID x 5 days x 5 days Abbas et al.121 1989 Ciprofloxacin Amoxicillin/ 102 87 No Open label Yes 350 mg BID clavulanic x 5 days acid 250/125 mg TID x 5 days Pisani et al.76 1996 Ciprofloxacin Lomefloxacin 139 155 Yes Double Yes 500 mg BID 400 mg OD x 15 days x 15 days Grubbs et al.93 1993 Ciprofloxacin TMP/SMX 103 100 No Double Yes 250 mg BID 160/800 mg x 10 days BID x 10 days Cox et al.98 1992 Ciprofloxacin Lomefloxacin 75 75 No Single Yes 500 mg BID 400 mg OD x 14 days x 14 days Stein et al.100 1992 Ciprofloxacin Temafloxacin 207 197 Yes Double Yes 250 mg BID 400 mg OD x 3 days x 3 days Ploubiec et al.124 1988 Ciprofloxacin Cefalexin 30 30 No Double Yes 250 mg BID 1 g BID x 3 days x 3 days
217 Gaceta Médica de México. 2015;151 NR NR (%) 0.05 0.02 0.02 0.11 0.13 0.05 0.21 0.04 0.08 0.07 0.09 0.03 0.01 0.17 Bact. Bact. Resist. Resist. Control Control NR NR 0.06 0.01 0.07 0.15 0.15 0.11 0.11 0.04 0.03 0.02 0.09 0.04 0.01 0.00 at the end of of end the at treatment with with treatment ciprofloxacin (%) (%) ciprofloxacin Bacterial resistance resistance Bacterial © Permanyer Publications 2015 NR NR NR NR NR NR NR NR NR NR NR NR (%) 0.86 0.99 0.84 0.87 0.86 0.81 Post- Post- .rehsilbup eht fo noissimrep nettirw roirp eht tuohtiw gniypocotohp ro decudorper eb yam noitacilbup siht fo trap oN trap fo siht noitacilbup yam eb decudorper ro gniypocotohp tuohtiw eht roirp nettirw noissimrep fo eht .rehsilbup Control Control Clin. cure cure Clin. NR NR NR NR NR NR NR NR NR NR NR NR 0.88 0.89 0.74 0.88 0.85 0.81 treatment with with treatment Maintenance of of Maintenance ciprofoxacin (%) ciprofoxacin clinical cure after after cure clinical NR NR NR NR NR NR NR NR NR NR (%) 0.86 0.96 0.66 0.64 0.75 0.76 0.63 0.69 Post- Control Control Bact. err. err. Bact. NR NR NR NR NR NR NR NR NR NR 0.89 0.88 0.65 0.65 0.63 0.79 0.67 0.65 treatment with with treatment Maintenance of of Maintenance ciprofoxacin (%) ciprofoxacin erradication after after erradication NR NR NR NR (%) End End 0.91 0.99 0.69 0.70 0.92 0.97 0.66 0.80 0.89 0.95 0.97 0.90 Control Control Clin. cure cure Clin. NR NR NR 0.87 0.89 0.70 0.70 0.93 0.97 0.76 0.89 0.85 0.91 0.76 0.96 0.95 the end of of end the treatment with with treatment Clinical cure at at cure Clinical ciprofloxacin (%) ciprofloxacin (%) 0.88 0.95 0.98 0.76 0.72 0.92 0.87 0.48 0.81 0.73 0.88 0.57 0.66 0.87 0.91 0.97 0.97 0.80 Bact. Bact. Control Control err. End End err. 0.87 0.88 0.93 0.69 0.69 0.83 0.90 0.61 0.80 0.81 0.86 0.66 0.92 0.81 0.91 0.96 0.96 1.00 Bacteriological ciprofloxacin (%) ciprofloxacin erradication at the at erradication end of treatment with treatment of end 70 70 35 94 23 26 124 93 74 121 42 42 78 76 100 98 53 50 Authors Authors Peterson et al. Peterson Klausner et al. Klausner al. et Carmignani et al. Naber et al. Naber Cox et al. Raz al. et Frankenschmidt et al. Naber et al. Abbas al. et Pisani et al. Cox et al. Stein al. et Ploubiec Grubbs et al. et Grubbs Whitby et al. et Whitby al. et Schaeffer Frankenschmidt et al. et Frankenschmidt NR: not reported Table 5. Characteristics of the studies included in the meta-analysis (acute UTI) (acute meta-analysis the in included studies the of Characteristics 5. Table
218 P. Gutiérrez-Castrellón, et al.: Ciprofloxacin and urinary tract infections in adults
Ciprofloxacin Control group group % Author, year, comparator RR (95% CI) n1 n2 Weight
Abbas, 1989, amoxocillin/clavulanic 1.41 (1.20-1.65) 94/102 57/87 1.45 Ploubiec, 1988, cefalexine 1.24 (1.03-1.50) 30/30 24/30 1.17 Iravani, 1993, fleroxacin 1.00 (0.96-1.04) 196/204 173/180 5.20 Frankenschmidt, 1997, fleroxacin 1.27 (0.92-1.74) 40/66 32/67 0.46 Whitby, 1996, fleroxacin 0.98 (0.83-1.15) 37/43 37/42 1.44 Frankenschmidt, 1997, fleroxacin 0.99 (0.86-1.13) 86/108 83/103 1.92 Naber, 2004, gatifloxacin 0.88 (0.76-1.01) 176/360 184/331 1.76 Naber, 2004, gatifloxacin 0.96 (0.84-1.09) 129/188 130/181 1.95 Naber, 2004, gatifloxacin 1.02 (0.88-1.19) 176/360 177/371 1.64 Naber, 2004, gatifloxacin 0.91 (0.80-1.03) 129/188 143/189 2.10 Cox, 2004, gatifloxacin 0.89 (0.79-1.01) 62/75 61/66 2.13 Peterson, 2008, levofloxacin 0.98 (0.92-1.05) 209/241 234/265 4.05 Klausner, 2007, levofloxacin 0.92 (0.84-1.01) 78/89 77/81 3.02 Pissani, 1996, lomefloxacin 0.93 (0.84-1.03) 113/139 135/155 2.78 Cox, 1992, lomefloxacin 0.98 (0.92-1.05) 67/70 70/72 4.18 © Permanyer Publications 2015
.rehsilbup eht fo noissimrep nettirw roirp eht tuohtiw gniypocotohp ro decudorper eb yam noitacilbup siht fo trap oN trap fo siht noitacilbup yam eb decudorper ro gniypocotohp Iravani, 1999, nitrofurantointuohtiw eht roirp nettirw 1.15 (1.04-1.26) 148/168 noissimrep 153/199fo 2.96 eht .rehsilbup Pfau, 1993, norfloxacin 1.10 (0.99-1.23) 56/58 50/57 2.53 Schaeffer, 1992, norfloxacin 1.16 (0.80-1.68) 23/35 21/37 0.35 Auqer, 2002, norfloxacin 0.99 (0.92-1.07) 104/114 103/112 3.52 Iravani, 1996, norfloxacin 0.95 (0.89-1.02) 134/149 133/141 4.00 Pfau, 1993, ofloxacin 1.00 (0.93-1.07) 56/58 57/59 3.96 McCarty, 1999, ofloxacin 1.02 (0.97-1.07) 215/228 211/228 4.83 Raz, 2000, ofloxacin 1.03 (0.95-1.12) 136/151 130/149 3.44 Carmignani, 2005, prulifloxacin 0.95 (0.90-1.01) 100/107 99/101 4.44 Naber 1996, esparfloxacin 1.12 (1.02-1.23) 215/264 183/252 2.93 Henry, 1999, esparfloxacin 1.05 (1.00-1.11) 154/159 151/164 4.64 Henry, 1999, esparfloxacin 1.04 (0.99-1.10) 154/159 155/167 4.74 Henry, 1986, TMP/SMX 1.06 (0.96-1.17) 31/31 32/34 2.73 Grubbs, 1992, TMP/SMX 1.00 (0.90-1.10) 69/76 62/68 2.69 Gomolin, 2002, TMP/SMX 1.11 (0.99-1.24) 82/88 68/81 2.47 McCarthy, 1999, TMP/SMX 0.97 (0.93-1.01) 215/228 224/230 5.29 Iravani, 1999, TMP/SMX 0.95 (0.89-1.02) 148/168 161/174 3.89 Stein, 1992, temafloxacin 0.99 (0.96-1.03) 199/207 191/197 5.35 Total (I2 = 59.2%; p = 0.000); z = 0.65; p = 0.51 1.01 (0.99-1.03) 3,861/4,711 3,801/4,670 100.00
Random effects model
0.574 1 1. 74 Ciprofloxacin Comparator
Figure 1. Ciprofloxacin efficacy in adult UTIs: end-of-treatment bacteriological erradication (overall).
Ciprofloxacin Control group group % Author, year, comparator RR (95% CI) n1 n2 Weight
Iravani, 1993, fleroxacin 1.00 (0.97-1.04) 199/204 175/180 8.56 Frankenschmidt, 1997, fleroxacin 1.15 (0.93-1.44) 50/66 44/67 0.48 Whitby, 1996, fleroxacin 0.95 (0.85-1.08) 39/43 38/40 1.52 Frankenschmidt, 1997, fleroxacin 0.99 (0.86-1.14) 85/108 82/103 1.16 Naber, 2004, gatifloxacin 0.99 (0.93-1.05) 304/360 316/371 4.40 Naber, 2004, gatifloxacin 1.00 (0.87-1.15) 131/188 126/181 1.22 Naber, 2004, gatifloxacin 1.04 (0.97-1.11) 304/360 301/371 3.96 Naber, 2004, gatifloxacin 1.01 (0.89-1.16) 131/188 130/189 1.22 Cox, 2004, gatifloxacin 1.01 (0.92-1.11) 70/75 61/66 2.38 Peterson, 2008, levofloxacin 0.95 (0.90-1.01) 210/241 242/265 4.43 Klausner, 2007, levofloxacin 0.90 (0.83-0.97) 79/89 80/81 3.11 Pissani, 1996, lomefloxacin 0.90 (0.80-1.00) 106/139 132/155 1.65 Cox, 1992, lomefloxacin 0.98 (0.92-1.05) 67/70 70/72 4.23 Iravani, 1999, nitrofurantoin 1.03 (0.97-1.08) 160/168 166/179 5.31 Auqer, 2002, norfloxacin 1.06 (0.93-1.21) 123/164 114/161 1.25 Iravani, 1996, norfloxacin 0.99 (0.95-1.04) 143/148 135/139 6.98 McCarty, 1999, ofloxacin 0.98 (0.94-1.03) 211/226 217/228 6.36 Raz, 2000, ofloxacin 1.00 (0.96-1.04) 140/144 138/142 7.36 Naber 1996, esparfloxacin 0.96 (0.91-1.03) 258/302 264/298 4.35 Henry, 1999, esparfloxacin 0.99 (0.94-1.05) 228/257 318/355 4.94 Henry, 1999, esparfloxacin 0.95 (0.91-1.01) 228/257 327/352 5.41 Gomolin, 2002, TMP/SMX 1.14 (1.03-1.25) 83/86 73/86 2.14 McCarthy, 1999, TMP/SMX 0.97 (0.93-1.01) 211/226 222/231 6.68 Iravani, 1999, TMP/SMX 1.00 (0.96-1.05) 160/168 165/174 5.92 Stein, 1992, temafloxacin 1.06 (1.00-1.12) 197/207 177/197 4.96 Total (I2 = 32.4%; p = 0.062); z = 0.78; p = 0.44 0.99 (0.98-1.01) 3,917/4,484 4,113/4,683 100.00
Random effects model
0.695 1 1.44
Figure 2. Ciprofloxacin efficacy in adult UTIs: end-of-treatment clinical resolution (overall). 219 Gaceta Médica de México. 2015;151
Ciprofloxacin Control group group % Author, year, comparator RR (95% CI) n1 n2 Weight
Iravani, 1993, fleroxacin 1.05 (0.94-1.17) 56/60 56/63 5.69 Whitby, 1996, fleroxacin 0.94 (0.70-1.27) 28/43 29/42 1.25 Naber, 2004, gatifloxacin 1.04 (0.89-1.22) 171/360 169/371 3.66 Naber, 2004, gatifloxacin 1.01 (0.87-1.18) 119/183 108/168 3.68 Naber, 2004, gatifloxacin 1.06 (0.90-1.23) 171/360 167/371 3.64 Naber, 2004, gatifloxacin 0.99 (0.85-1.15) 119/183 122/186 3.90 Cox, 2004, gatifloxacin 0.83 (0.66-1.06) 39/62 46/61 1.85 Peterson, 2008, levofloxacin 1.04 (0.97-1.11) 215/241 228/265 8.96 Klausner, 2007, levofloxacin 0.91 (0.83-0.99) 78/89 78/81 7.09 Iravani, 1999, nitrofurantoin 1.11 (1.01-1.22) 118/130 115/141 6.61 Iravani, 1996, norfloxacin 0.89 (0.79-0.99) 91/114 99/110 5.64 McCarty, 1999, ofloxacin 1.06 (0.98-1.15) 173/194 155/184 7.81
Raz, 2000, ofloxacin 1.04 (0.92-1.18) 114/144 108/142 4.93 © Permanyer Publications 2015 Naber 1996, esparfloxacin 1.07 (0.94-1.22) 174/258 161/256 4.83 .rehsilbup eht fo noissimrep nettirw roirp eht tuohtiw gniypocotohp ro decudorper eb yam noitacilbup siht fo trap oN trap fo siht noitacilbup yam eb decudorper ro gniypocotohp tuohtiw eht roirp nettirw noissimrep fo eht .rehsilbup Henry, 1999, esparfloxacin 1.04 (0.97-1.11) 147/159 146/164 8.60 Henry, 1999, esparfloxacin 1.15 (1.05-1.25) 147/159 134/166 7.26 McCarthy, 1999, TMP/SMX 1.02 (0.95-1.10) 173/194 175/201 8.37 Iravani, 1999, TMP/SMX 1.16 (1.04-1.28) 118/130 113/144 6.23 Total (I2 = 47.2%; p = 0.014); z = 1.85; p = 0.06 1.03 (1.00-1.27) 2,251/3,063 2,209/3,116 100.00
Random effects model
0.657 1 1.52
Figure 3. Ciprofloxacin efficacy in adult UTIs: bacteriological erradication after treatment (overall).
Ciprofloxacin Control Author, year, comparator group group % RR (95% CI) n1 n2 Weight Whitby, 1996, fleroxacin 1.01 (0.82-1.23) 35/43 34/42 1.20 Naber, 2004, gatifloxacin 0.97 (092-1.03) 309/360 327/371 8.53 Naber, 2004, gatifloxacin 1.05 (0.99-1.12) 309/360 303/371 7.44 Cox, 2004, gatifloxacin 0.89 (0.74-1.06) 52/70 51/61 1.57 Peterson, 2008, levofloxacin 1.02 (0.96-1.09) 213/241 229/265 7.15 Klausner, 2007, levofloxacin 0.90 (0.83,0.97) 79/89 81/82 5.86 Iravani, 1999, nitrofurantoin 0.97 (0.90-1.04) 132/147 166/179 6.90 Auqer, 2002, norfloxacin 0.96 (0.89-1.03) 104/114 105/110 6.69 Iravani, 1996, norfloxacin 0.93 (0.87-1.00) 121/136 125/131 6.68 McCarty, 1999, ofloxacin 1.00 (0.94-1.06) 184/203 184/203 7.62 Raz, 2000, ofloxacin 1.00 (0.92-109) 126/144 124/142 4.95 Naber 1996, esparfloxacin 0.99 (0.92-1.06) 229/270 230/268 6.68 Henry, 1999, esparfloxacin 1.00 (0.92-1.09) 191/236 182/225 4.89 Henry, 1999, esparfloxacin 1.03 (0.94-1.13) 191/236 184/234 4.71 Gomolin, 2002, TMP/SMX 1.11 (1.00-1.22) 74/76 59/67 4.39 McCarthy, 1999, TMP/SMX 1.01 (0.95-1.08) 184/203 186/208 7.38 Iravani, 1999, TMP/SMX 0.95 (0.89-1.01) 132/147 165/174 7.35 Total (I2 = 36.2%; p = 0.068); z = 1.08; p = 0.28 0.99 (0.96-1.01) 2,665/3,075 2,735/3,133 100.00
Random effects model
0.744 1 1.34
Figura 4. Ciprofloxacin efficacy in adult UTIs: clinical resolution after treatment (overall). 220 P. Gutiérrez-Castrellón, et al.: Ciprofloxacin and urinary tract infections in adults
Ciprofloxacin Control group group % Author, year, comparator RR (IC 95%) n1 n2 Weight
Abbas, 1989, amoxocillin/clavulanic 0.28 (0.06-1.37) 2/102 6/87 1.91 Ploubiec, 1988, cefalexine 0.09 (0.01-1.52) 0/30 5/29 0.63 Iravani, 1993, fleroxacin 0.97 (0.36-2.63) 8/204 7/174 4.11 Frankenschmidt, 1997, fleroxacin 0.51 (0.22-1.18) 7/66 14/67 5.26 Frankenschmidt, 1997, fleroxacin 0.95 (0.24-3.71) 4/108 4/103 2.47 Naber, 2004, gatifloxacin 1.15 (0.61-2.18) 19/360 17/371 7.48 Naber, 2004, gatifloxacin 1.12 (0.68-1.86) 28/188 24/181 9.50 Naber, 2004, gatifloxacin 1.22 (0.64-2.34) 19/360 16/371 7.33 Naber, 2004, gatifloxacin 1.34 (0.79-2.27) 28/188 21/189 9.12 Cox, 2004, gatifloxacin 2.22 (0.60-8.21) 7/64 3/61 2.64 Peterson, 2008, levofloxacin 1.28 (0.61-2.72) 14/241 12/265 6.13 Klausner, 2007, levofloxacin 0.54 (0.05-5.87) 1/82 2/89 0.89 Cox, 1992, lomefloxacin 1.50 (0.26-8.72) 3/75 2/75 1.56
Iravani, 1999, nitrofurantoin 0.92 (0.52-1.61) 20/168 23/177 8.60 © Permanyer Publications 2015 Schaeffer, 1992, norfloxacin 0.35 (0.04-3.23) 1/35 3/37 1.02 .rehsilbup eht fo noissimrep nettirw roirp eht tuohtiw gniypocotohp ro decudorper eb yam noitacilbup siht fo trap oN trap fo siht noitacilbup yam eb decudorper ro gniypocotohp Iravani, 1996, norfloxacintuohtiw eht roirp nettirw 1.10 (0.38-3.21) 7/149noissimrep 6/141fo 3.69 eht .rehsilbup McCarty, 1999, ofloxacin 0.56 (0.25-1.25) 9/228 16/228 5.67 Carmignani, 2005, prulifloxacin 3.30 (0.70-15.53) 7/107 2/101 1.97 Grubbs, 1992, TMP/SMX 1.04 (0.37-2.95) 7/76 6/68 3.84 Gomolin, 2002, TMP/SMX 0.27 (0.11-0.66) 6/167 22/167 4.96 McCarthy, 1999, TMP/SMX 1.51 (0.55-4.18) 9/228 6/230 3.97 Iravani, 1999, TMP/SMX 2.07 (1.00-4.29) 20/168 10/174 6.37 Stein, 1992, temafloxacin 1.90 (0.17-20.82) 2/207 1/197 0.88 Total (I2 = 27.8%; p = 0.107); z = 0.05, p = 0.96 1.01 (0.80-1.27) 228/3,601 228/3,582 100.00
Random effects model
0.00508 1 197
Figure 5. Ciprofloxacin efficacy in adult UTIs: end-of-treatment bacterial resistances (global).
Ciprofloxacin Control group group % Author, year, comparator RR (95% CI) n1 n2 Weight
Abbas, 1989, amoxocillin/clavulanic 0.43 (0.08-2.27) 2/102 4/87 0.33 Iravani, 1993, fleroxacin 0.86 (0.67-1.10) 84/324 97/321 5.14 Frankenschmidt, 1997, fleroxacin 1.12 (0.60-2.09) 17/84 15/83 1.88 Whitby, 1996, fleroxacin 1.05 (0.52-2.08) 13/65 13/68 1.62 Frankenschmidt, 1997, fleroxacin 0.72 (0.42-1.23) 18/115 26/119 2.30 Naber, 2004, gatifloxacin 0.75 (0.54-1.05) 52/360 71/371 4.15 Naber, 2004, gatifloxacin 1.15 (0.86-1.54) 64/267 78/374 4.58 Naber, 2004, gatifloxacin 0.84 (0.60-1.17) 52/360 64/371 4.05 Naber, 2004, gatifloxacin 0.47 (0.36-0.60) 64/366 143/382 5.01 Cox, 2004, gatifloxacin 0.54 (0.27-1.09) 11/183 21/189 1.58 Peterson, 2008, levofloxacin 0.63 (0.55-0.73) 122/255 185/244 6.51 Klausner, 2007, levofloxacin 0.89 (0.69-1.16) 65/166 64/146 4.93 Cox, 1992, lomefloxacin 1.14 (0.60-2.17) 16/75 14/75 1.81 Iravani, 1999, nitrofurantoin 0.83 (0.63-1.08) 68/243 80/236 4.86 Schaeffer, 1992, norfloxacin 1.06 (0.38-2.97) 6/35 6/37 0.82 Auqer, 2002, norfloxacin 1.03 (0.58-1.84) 21/124 18/110 2.13 Iravani, 1996, norfloxacin 0.98 (0.58-1.63) 25/210 26/213 2.48 McCarty, 1999, ofloxacin 0.81 (0.65-1.01) 90/270 121/295 5.56 Raz, 2000, ofloxacin 0.81(0.49-1.32) 25/230 31/230 2.62 Carmignani, 2005, prulifloxacin 0.91 (0.58-1.43) 27/107 28/101 2.92 Naber 1996, esparfloxacin 0.79 (0.45-1.36) 21/340 27/344 2.27 Henry, 1999, esparfloxacin 0.99 (0.87-1.12) 212/386 219/394 6.76 Henry, 1999, esparfloxacin 1.02 (0.90-1.16) 212/386 212/395 6.73 Henry, 1986, TMP/SMX 0.33 (0.10-1.09) 3/31 10/34 0.63 Grubbs, 1992, TMP/SMX 0.55 (0.33-0.91) 18/103 32/100 2.53 Gomolin, 2002, TMP/SMX 0.70 (0.43-1.14) 22/129 32/132 2.68 McCarthy, 1999, TMP/SMX 0.86 (0.69-1.07) 90/270 113/290 5.50 Iravani, 1999, TMP/SMX 0.74 (0.57-0.95) 68/243 90/237 4.99 Stein, 1992, temafloxacin 1.23 (0.75-2.02) 31/207 24/197 2.61 Total (I2 = 60.1%; p = 0.000); z = 3.8; p = 0.0001 0.82 (0.75-0.91) 1,519/6,036 1,864/6,175 100.00
Random effects model
0.08 1 12.5
Figure 6. Ciprofloxacin safety in adult UTIs: risk of adverse events (overall). 221 Gaceta Médica de México. 2015;151
Ciprofloxacin Control group group % Author, year, comparator RR (95% CI) n1 n2 Weight
Abbas, 1989, amoxocillin/clavulanic 1.41 (1.20-1.65) 94/102 57/87 3.74 Ploubiec, 1988, cefalexine 1.24 (1.03-1.50) 30/30 24/30 3.10 Frankenschmidt, 1997, fleroxacin 1.27 (0.92-1.74) 40/66 32/67 1.33 Whitby, 1996, fleroxacin 0.98 (0.83-1.15) 37/43 37/42 3.70 Frankenschmidt, 1997, fleroxacin 0.99 (0.86-1.13) 86/108 83/103 4.70 Naber, 2004, gatifloxacin 0.96 (0.84-1.09) 129/188 130/181 4.76 Naber, 2004, gatifloxacin 0.91 (0.80-1.03) 129/188 143/189 5.04 Cox, 2004, gatifloxacin 0.89 (0.79-1.01) 62/75 61/66 5.10 Peterson, 2008, levofloxacin 0.98 (0.92-1.05) 209/241 234/265 8.13 Klausner, 2007, levofloxacin 0.92 (0.84-1.01) 78/89 77/81 6.65 Pissani, 1996, lomefloxacin 0.93 (0.84-1.03) 113/139 135/155 6.25 Cox, 1992, lomefloxacin 0.98 (0.92-1.05) 67/70 70/72 8.30 Schaeffer, 1992, norfloxacin 1.16 (0.80-1.68) 23/35 21/37 1.01 Raz, 2000, ofloxacin 1.03 (0.95-1.12) 136/151 130/149 7.28 Carmignani, 2005, prulifloxacin 0.95 (0.90-1.01) 100/107 99/101 8.63 © Permanyer Publications 2015
.rehsilbup eht fo noissimrep nettirw roirp eht tuohtiw gniypocotohp ro decudorper eb yam noitacilbup siht fo trap oN trap fo siht noitacilbup yam eb decudorper ro gniypocotohp Naber 1996, esparfloxacintuohtiw eht roirp nettirw 1.12 (1.02-1.23) 215/264 noissimrep 183/252fo 6.50 eht .rehsilbup Grubbs, 1992, TMP/SMX 1.00 (0.90-1.10) 69/76 62/68 6.11 Stein, 1992, temafloxacin 0.99 (0.96-1.03) 199/207 191/197 9.68 Total (I2 = 64.2%; p = 0.000); z = 0.10; p = 0.92 1.00 (0.96-1.04) 1,816/2,179 1,769/2,142 100.00
Random effects model
0.574 Ciprofloxacin 1 Comparator 1.75
Figure 7. Ciprofloxacin efficacy in UTIs in adults with risk factors: end-of-treatment bacteriological erradication (overall).
Ciprofloxacin Control group group % Author, year, comparator RR (95% CI) n1 n2 Weight
Frankenschmidt, 1997, fleroxacin 1.15 (0.93-1.44) 50/66 44/67 1.59 Whitby, 1996, fleroxacin 0.95 (0.85-1.08) 39/43 38/40 4.67 Frankenschmidt, 1997, fleroxacin 0.99 (0.86-1.14) 85/108 82/103 3.65 Naber, 2004, gatifloxacin 1.00 (0.87-1.15) 131/188 126/181 3.82 Naber, 2004, gatifloxacin 1.01 (0.89-1.16) 131/188 130/189 3.83 Cox, 2004, gatifloxacin 1.01 (0.09-1.11) 70/75 61/66 6.91 Peterson, 2008, levofloxacin 0.95 (0.90-1.01) 210/241 242/265 11.33 Klausner, 2007, levofloxacin 0.90 (0.83-0.97) 79/89 80/81 8.61 Pissani, 1996, lomefloxacin 0.90 (0.80-1.00) 106/139 132/155 5.03 Cox, 1992, lomefloxacin 0.98 (0.92-1.05) 67/70 70/72 10.95 Raz, 2000, ofloxacin 1.00 (0.96-1.04) 140/144 138/142 16.11 Naber 1996, esparfloxacin 0.96 (0.91-1.03) 258/302 264/298 11.18 Stein, 1992, temafloxacin 1.06 (1.00-1.12) 197/207 177/197 12.31 Total (I2 = 38.0%; p = 0.081); z = 1.2; p = 0.22 0.98 (0.95-1.01) 1,563/1,860 1,584/1,856 100.00
Random effects model
0.695 Ciprofloxacin 1 Comparator 1.44
Figure 8. Ciprofloxacin efficacy in UTIs in adults with risk factors: end-of-treatment clinical cure (overall).
Ciprofloxacin Control group group % Author, year, comparator RR (95% CI) n1 n2 Weight
Whitby, 1996, fleroxacin 0.94 (0.70-1.27) 28/43 29/42 2.91 Naber, 2004, gatifloxacin 1.01 (0.87-1.18) 119/183 108/168 9.28 Naber, 2004, gatifloxacin 0.99 (0.85-1.15) 119/183 122/186 9.90 Cox, 2004, gatifloxacin 0.83 (0.66-1.06) 39/62 46/61 4.39 Peterson, 2008, levofloxacin 1.04 (0.97-1.11) 215/241 228/265 27.63 Klausner, 2007, levofloxacin 0.91 (0.83-0.99) 78/89 78/81 20.25 Raz, 2000, ofloxacin 1.04 (0.92-1.18) 114/144 108/142 12.97 Naber 1996, esparfloxacin 1.07 (0.94-1.22) 174/258 161/256 12.67 Total (I2 = 27.4%; p = 0.210); z = 0.17; p = 0.87 1.00 (0.94-1.05) 886/1,203 880/1,201 100.00
Random effects model
0.657 Ciprofloxacin 1 Comparator 1.52
Figure 9. Ciprofloxacin efficacy in UTIs in adults with risk factors: bacteriological erradication after treatment. 222 P. Gutiérrez-Castrellón, et al.: Ciprofloxacin and urinary tract infections in adults
Ciprofloxacin Control Group Group % Author, year, comparator RR (95% CI) n1 n2 Weight
Whitby, 1996, fleroxacin 1.01 (0.82-1.23) 35/43 34/42 5.02 Cox, 2004, gatifloxacin 0.89 (0.74-1.06) 52/70 51/61 6.49 Peterson, 2008, levofloxacin 1.02 (0.96-1.09) 213/241 229/265 25.05 Klausner, 2007, levofloxacin 0.90 (0.83-0.97) 79/89 81/82 21.29 Raz, 2000, ofloxacin 1.00 (0.92-1,09) 126/144 124/142 18.46 Naber, 1996, esparfloxacin 0.99 (0.92-1.06) 229/270 230/268 23.69 Total (I2 = 37.9%; p = 0.153); z = 1.09; p = 0.28 0.97 (0.93-1.02) 734/857 749/860 100.00
Random effects model
0.744 Ciprofloxacin 1 Comparator 1.34 © Permanyer Publications 2015 .rehsilbup eht fo noissimrep nettirw roirp eht tuohtiw gniypocotohp ro decudorper eb yam noitacilbup siht fo trap oN trap fo siht noitacilbup yam eb decudorper ro gniypocotohp tuohtiw eht roirp nettirw noissimrep fo eht .rehsilbup Figure 10. Ciprofloxacin efficacy in UTIs in adults with risk factors: clinical cure after treatment.
Ciprofloxacin Control group group % Author, year, comparator RR (95% CI) n1 n2 Weight
Abbas, 1989, amoxocillin/clavulanic 0.28 (0.06-1.37) 2/102 6/87 3.41 Ploubiec, 1988, cefalexine 0.09 (0.01-1.52) 0/30 5/29 1.08 Frankenschmidt, 1997, fleroxacin 0.51 (0.22-1.18) 7/66 14/67 10.58 Frankenschmidt, 1997, fleroxacin 0.95 (0.24-3.71) 4/108 4/103 4.49 Naber, 2004, gatifloxacin 1.12 (0.68-1.86) 28/188 24/181 22.87 Naber, 2004, gatifloxacin 1.34 (0.79-2.27) 28/188 21/189 21.56 Cox, 2004, gatifloxacin 2.22 (0.60-8.21) 7/64 3/61 4.84 Peterson, 2008, levofloxacin 1.28 (0.61-2.72) 14/241 12/265 12.76 Klausner, 2007, levofloxacin 0.54 (0.05-5.87) 1/82 2/89 1.53 Cox, 1992, lomefloxacin 1.50 (0.26-8.72) 3/75 2/75 2.75 Schaeffer, 1992, norfloxacin 0.35 (0.04-3.23) 1/35 3/37 1.77 Carmignani, 2005, prulifloxacin 3.30 (0.70-15.53) 7/107 2/101 3.52 Grubbs, 1992, TMP/SMX 1.04 (0.37-2.95) 7/76 6/68 7.32 Stein, 1992, temafloxacin 1.90 (0.17-20.82) 2/207 1/197 1.52 Total (I2 = 11.1%; p = 0.332); z = 0.37; p = 0.51 1.06 (0.78-1.42) 111/1,569 105/1,549 100.00
Random effects model
0.00508 Ciprofloxacin 1 Comparator 197
Figure 11. Ciprofloxacin efficacy in UTIs in adults with risk factors: bacterial resistances.
Ciprofloxacin Control group group % Author, year, comparator RR (95% CI) n1 n2 Weight
Abbas, 1989, amoxocillin/clavulanic 0.43 (0.08-2.27) 2/102 4/87 1.05 Frankenschmidt, 1997, fleroxacin 1.12 (0.60-2.09) 17/84 15/83 4.95 Whitby, 1996, fleroxacin 1.05 (0.52-2.08) 13/65 13/68 4.37 Frankenschmidt, 1997, fleroxacin 0.72 (0.42-1.23) 18/115 26/119 5.80 Naber, 2004, gatifloxacin 1.15 (0.86-1.54) 64/267 78/374 9.40 Naber, 2004, gatifloxacin 0.47 (0.36-0.60) 64/366 143/382 9.93 Cox, 2004, gatifloxacin 0.54 (0.27-1.09) 11/183 21/189 4.28 Peterson, 2008, levofloxacin 0.63 (0.55-0.73) 122/255 185/244 11.55 Klausner, 2007, levofloxacin 0.89 (0.69-1.16) 65/166 64/146 9.83 Cox, 1992, lomefloxacin 1.14 (0.60-2.17) 16/75 14/75 4.79 Schaeffer, 1992, norfloxacin 1.06 (0.38-2.97) 6/35 6/37 2.42 Raz, 2000, ofloxacin 0.81 (0.49-1.32) 25/230 31/230 6.39 Carmignani, 2005, prulifloxacin 0.91 (0.58-1.43) 27/107 28/101 6.93 Naber 1996, esparfloxacin 0.79 (0.45-1.36) 21/340 27/344 5.72 Grubbs, 1992, TMP/SMX 0.55 (0.33-0.91) 18/103 32/100 6.23 Stein, 1992, temafloxacin 1.23 (0.75-2.02) 31/207 24/197 6.37 Total (I2 = 62.6%; p = 0.000); z = 2.46; p = 0.01 0.80 (0.67-0.96) 520/2,700 711/2,776 100.00
Random effects model
0.08 1 12.5 Ciprofloxacin Comparator
Figure 12. Ciprofloxacin safety in UTIs in adults with risk factors: risk of related adverse events. 223 Gaceta Médica de México. 2015;151
Ciprofloxacin Control group group % Author, year, comparator RR (95% CI) n1 n2 Weight
Iravani, 1993, fleroxacin 1.00 (0.96-1.04) 196/204 173/180 10.45 Naber, 2004, gatifloxacin 0.88 (0.76-1.01) 176/360 184/331 2.79 Naber, 2004, gatifloxacin 1.02 (0.88-1.19) 176/360 177/371 2.58 Iravani, 1999, nitrofurantoin 1.15 (1.04-1.26) 148/168 153/199 5.07 Pfau, 1993, norfloxacin 1.10 (0.99-1.23) 56/58 50/57 4.21 Auqer, 2002, norfloxacin 0.99 (0.92-1.07) 104/114 103/112 6.25 Iravani, 1996, norfloxacin 0.95 (0.89-1.02) 134/149 133/141 7.35 Pfau, 1993, ofloxacin 1.00 (0.93-1.07) 56/58 57/59 7.25 McCarty, 1999, ofloxacin 1.02 (0.97-1.07) 215/228 211/228 9.43 Henry, 1999, esparfloxacin 1.05 (1.00-1.11) 154/159 151/164 8.93 Henry, 1999, esparfloxacin 1.04 (0.99-1.10) 154/159 155/167 9.20 Henry, 1986, TMP/SMX 1.06 (0.96-1.17) 31/31 32/34 4.60 Gomolin, 2002, TMP/SMX 1.11(0.99-1.24) 82/88 68/81 4.09
McCarthy, 1999, TMP/SMX 0.97 (0.93-1.01) 215/228 224/230 10.71 © Permanyer Publications 2015 Iravani, 1999, TMP/SMX 0.95 (0.89-1.02) 148/168 161/174 7.09 .rehsilbup eht fo noissimrep nettirw roirp eht tuohtiw gniypocotohp ro decudorper eb yam noitacilbup siht fo trap oN trap fo siht noitacilbup yam eb decudorper ro gniypocotohp Total (I2 = 55.4%; p = 0.005);tuohtiw z = 1.0;eht p = 0.30 roirp nettirw 1.01 (0.99-1.04) 2,045/2,532 noissimrep 2,032/2,528 fo 100.00 eht .rehsilbup
Random effects model
0.762 1 1.31 Ciprofloxacin Comparator
Figure 13. Ciprofloxacin efficacy in acute UTIs in adults: end-of-treatment bacteriological erradication.
Ciprofloxacin Control group group % Author, year, comparator RR (95% CI) n1 n2 Weight
Iravani, 1993, fleroxacin 1.00 (0.97-1.04) 199/204 175/180 14.99 Naber, 2004, gatifloxacin 0.99 (0.93-1.05) 304/360 316/371 6.78 Naber, 2004, gatifloxacin 1.04 (0.97-1.11) 304/360 301/371 6.04 Iravani, 1999, nitrofurantoin 1.03 (0.97-1.08) 160/168 166/179 8.40 Auqer, 2002, norfloxacin 1.06 (0.93-1.21) 123/164 114/161 1.77 Iravani, 1996, norfloxacin 0.99 (0.95-1.04) 143/148 135/139 11.62 McCarty, 1999, ofloxacin 0.98 (0.94-1.03) 211/226 217/228 10.40 Henry, 1999, esparfloxacin 0.99 (0.94-1.05) 228/257 318/355 7.74 Henry, 1999, esparfloxacin 0.95 (0.91-1.01) 228/257 327/352 8.59 Gomolin, 2002, TMP/SMX 1.14 (1.03-1.25) 83/86 73/86 3.11 McCarthy, 1999, TMP/SMX 0.97 (0.93-1.01) 211/226 222/231 11.02 Iravani, 1999, TMP/SMX 1.00 (0.96-1.05) 160/168 165/174 9.55 Total (I2 = 29.9%; p = 0.153); z = 0.5; p = 0.96 1.00 (0.98-1.02) 2,354/2,624 2,529/2,827 100.00
Random effects model
0.798 1 1.25 Ciprofloxacin Comparator
Figure 14. Ciprofloxacin efficacy in acute UTIs in adults: end-of treatment-clinical cure.
Ciprofloxacin Control group group % Author, year, comparator RR (95% CI) n1 n2 Weight
Iravani, 1993, fleroxacin 1.05 (0.94-1.17) 56/60 56/63 8.92 Naber, 2004, gatifloxacin 1.04 (0.89-1.22) 171/360 169/371 5.70 Naber, 2004, gatifloxacin 1.06 (0.90-1.23) 171/360 167/371 5.65 Iravani, A1B1999, nitrofurantoin 1.11 (1.01-1.22) 118/130 115/141 10.41 Iravani, 1996, norfloxacin 0.89 (0.79-0.99) 91/114 99/110 8.83 McCarty, 1999, ofloxacin 1.06 (0.98-1.15) 173/194 155/184 12.35 Henry, 1999, esparfloxacin 1.04 (0.97-1.11) 147/159 146/164 13.64 Henry, 1999, esparfloxacin 1.15 (1.05-1.25) 147/159 134/166 11.46 McCarthy, 1999, TMP/SMX 1.02 (0.95-1.10) 173/194 175/201 13.27 Iravani, 1999, TMP/SMX 1.16 (1.04-1.28) 118/130 113/144 9.78 Total (I2 = 50.0%; p = 0.035); z = 2.5; p = 0.01 1.06 (1.01-1.10) 1,365/1,860 1,329/1,915 100.00
Random effects model
0.781 1 1.28 Ciprofloxacin Comparator
Figure 15. Ciprofloxacin efficacy in acute UTIs in adults: bacteriological erradication after treatment. 224 P. Gutiérrez-Castrellón, et al.: Ciprofloxacin and urinary tract infections in adults
Ciprofloxacin Control group group % Author, year, comparator RR (95% CI) n1 n2 Weight
Naber, 2004, Gatiflox 0.97 (0.92-1.03) 309/360 327/371 11.73 Naber, 2004, Gatiflox 1.05 (0.99-1.12) 309/360 303/371 10.24 Iravani, 1999, nitrofurantoin 0.97 (0.90-1.04) 132/147 166/179 9.51 Auqer, 2002, norfloxacin 0.96 (0.89-1.03) 104/114 105/110 9.21 Iravani, 1996, norfloxacin 0.93 (0.87-1.00) 121/136 125/131 9.21 McCarty, 1999, ofloxacin 1.00 (0.94-1.06) 184/203 184/203 10.49 Henry, 1999, esparfloxacin 1.00 (0.92-1.09) 191/236 182/225 6.75 Henry, 1999, esparfloxacin 1.03 (0.94-1.13) 191/236 184/234 6.50 Gomolin, 2002, TMP/SMX 1.11 (1.00-1.22) 74/76 59/67 6.06 McCarthy, 1999, TMP/SMX 1.01 (0.95-1.08) 184/203 186/208 10.17 Iravani, 1999, TMP/SMX 0.95 (0.89-1.01) 132/147 165/174 10.12 Total (I2 = 40.0%; p = 0.082); z = 0.51; p = 0.57 0.99 (0.97-1.02) 1,931/2,218 1,986/2,273 100.00
Random effects model © Permanyer Publications 2015 .rehsilbup eht fo noissimrep nettirw roirp eht tuohtiw gniypocotohp ro decudorper eb yam noitacilbup siht fo trap oN trap fo siht noitacilbup yam eb decudorper ro gniypocotohp tuohtiw eht roirp nettirw noissimrep fo eht .rehsilbup 0.822 Ciprofloxacin 1 Comparator 1.22
Figure 16. Ciprofloxacin efficacy in acute UTIs in adults: clinical cure after treatment.
Ciprofloxacin Control group group % Author, year, comparator RR (95% CI) n1 n2 Weight
Iravani, 1993, fleroxacin 0.97 (0.36-2.63) 8/204 7/174 8.54 Naber, 2004, gatifloxacin 1.15 (0.61-2.18) 19/360 17/371 13.66 Naber, 2004, gatifloxacin 1.22 (0.64-2.34) 19/360 16/371 13.46 Iravani, 1999, nitrofurantoin 0.92 (0.52-1.61) 20/168 23/177 15.10 Iravani, 1996, norfloxacin 1.10 (0.38-3.21) 7/149 6/141 7.80 McCarty, 1999, ofloxacin 0.56 (0.25-1.25) 9/228 16/228 11.08 Gomolin, 2002, TMP/SMX 0.27 (0.11-0.66) 6/167 22/167 9.95 McCarthy, 1999, TMP/SMX 1.51 (0.55-4.18) 9/228 6/230 8.30 Iravani, 1999, TMP/SMX 2.07 (1.00-4.29) 20/168 10/174 12.11 Total (I2 = 48.8%; p = 0.048); z = 0.17; p = 0.86 0.97 (0.67-1.39) 117/2,032 123/2,033 100.00
Random effects model
0.113 1 8.81 Ciprofloxacin Comparator
Figure 17. Ciprofloxacin efficacy in acute UTIs in adults: bacterial resistances.
Ciprofloxacin Control group group % Author, year, comparator RR (IC 95%) n1 n2 Weight
Iravani, 1993, fleroxacin 0.86 (0.67-1.10) 84/324 97/321 8.35 Naber, 2004, gatifloxacin 0.75 (0.54-1.05) 52/360 71/371 5.31 Naber, 2004, gatifloxacin 0.84 (0.60-1.17) 52/360 64/371 5.07 Iravani, 1999, nitrofurantoin 0.83 (0.63-1.08) 68/243 80/236 7.34 Auqer, 2002, norfloxacin 1.03 (0.58-1.84) 21/124 18/110 1.91 Iravani, 1996, norfloxacin 0.98 (0.58-1.63) 25/210 26/213 2.35 McCarty, 1999, ofloxacin 0.81 (0.65-1.01) 90/270 121/295 10.18 Henry, 1999, esparfloxacin 0.99 (0.87-1.12) 212/386 219/394 19.53 Henry, 1999, esparfloxacin 1.02 (0.90-1.16) 212/386 212/395 19.19 Henry, 1986, TMP/SMX 0.33 (0.10-1.09) 3/31 10/34 0.46 Gomolin, 2002, TMP/SMX 0.70 (0.43-1.14) 22/129 32/132 2.62 McCarthy, 1999, TMP/SMX 0.86 (0.69-1.07) 90/270 113/290 9.88 Iravani, 1999, TMP/SMX 0.74 (0.57-0.95) 68/243 90/237 7.80 Total (I2 = 23.2%; p = 0.209); z = 2.97; p = 0.003 0.88 (0.81-0.96) 999/3,336 1,153/3,399 100.00
Random effects model
0.0996 1 10
Figure 18. Ciprofloxacin efficacy in acute UTIs in adults: risk of related adverse events. 225 Gaceta Médica de México. 2015;151
8. Pohl A. Modes of administration of antibiotics for symptomatic severe Discussion and conclusions urinary tract infections. Cochrane Database Syst Rev. 2007;(4):CD003237. 9. Regal RE, Pham CQ, Bostwick TR. Urinary tract infections in extended care facilities: preventive management strategies. Consult Pharm. UTIs represent one of the most common conditions 2006;21(5):400-9. for which antibiotics are prescribed in primary care cen- 10. Lutters M, Vogt N. Antibiotic duration for treating uncomplicated, symp- tomatic lower urinary tract infections in elderly women. Cochrane Data- ters. Specifically, the use of co-trimoxazole as first-line base Syst Rev. 2002;(3):CD001535. 11. Hooton TM, Stamm WE. Management of acute uncomplicated urinary agent is recommended in areas with prevalence of re- tract infection in adults. Med Clin North Ame. 1991;75(2):339-57. sistance to this medication lower than 20%; in areas 12. Hooton TM, Stamm WE. Diagnosis and treatment of uncomplicated uri- nary tract infection. Infect Dis Clin North Am. 1997;11(2):551-81. where resistance exceeds this figure, treatment alterna- 13. Neu HC. Optimal characteristics of agents to treat uncomplicated urinary 131 tract infection. Infection. 1992;20 Suppl 4:S266-71. tives have to be considered . Available evidence at 14. Naber KG. Short-term therapy of acute uncomplicated cystitis. Curr Opin this moment indicates that ciprofloxacin is a safe and Urol. 1999;9(1):57-64. 15. Naber KG. Treatment options for acute uncomplicated cystitis in adults. efficacious alternative, with lower numbers of adverse J Antimicrob Chemother. 2000;46 Suppl 1:23-7.
events than other antimicrobials, for the treatment of 16. Warren JW, Abrutyn E, Hebel JR, Johnson JR, Schaeffer AJ, Stamm WE. © Permanyer Publications 2015
.rehsilbup eht fo noissimrep nettirw roirp eht tuohtiw gniypocotohp ro decudorper eb yam noitacilbup siht fo trap oN trap fo siht noitacilbup yam eb decudorper ro gniypocotohp tuohtiw eht roirp Guidelinesnettirw for antimicrobial treatmentnoissimrep offo uncomplicated eht acute bacterial .rehsilbup acute or complicated UTIs (associated with risk factors). cystitis and acute pyelonephritis in women. Infectious Diseases Society of America (IDSA). Clin Infect Dis. 1999;29(4):745-58. Methodological quality of the 30 studies included in the 17. Minassian MA, Lewis DA, Chattopadhyay D, Bovill B, Duckworth GJ, meta-analysis with adequate assignment of the maneu- Williams JD. A comparison between single-dose fosfomycin trometamol (Monuril) and a 5-day course of trimethoprim in the treatment of uncom- ver (allocation concealment), most of them double-blind- plicated lower urinary tract infection in women. Int J Antimicrob Agents. 1998;10(1):39-47. ed, allows for this recommendation to be supported. The 18. Sharma PC, Jain A, Jain S, Pahwa R, Yar MS. Ciprofloxacin: review on broad range of age in the groups (18-85 years), the developments in synthetic,analytical, and medicinal aspects. J Enzyme Inhib Med Chem. 2010;25(4):577-89 inclusion of patients of both genders and the presence 19. Mirone V, Fusco F, Taglialatela D, et al. Efficacy and safety of ciproflox- acin XR 1000 mg once daily versus ciprofloxacin 500 mg twice daily in of different microorganisms, as well as the employed the treatment of complicated urinary tract infections. J Chemother. doses of different antimicrobials in both groups and its 2009;21(6):651-60. 20. Pfefferkorn U, Lea S, Moldenhauer J, Peterli R, von Floe M, Ackermann duration, generated a variable heterogeneity in the C. Antibiotic prophylaxis at urinary catheter removal prevents urinary tract study, which, although partially adjusted by using ran- infections: a prospective randomized trial. Ann Surg. 2009;249(4): 573-5. 21. Cam K, Kayikci A, Akman Y, Erol A. Prospective assessment of the ef- dom effects models (inverse of the variance), has to be ficacy of single dose versus traditional 3-day antimicrobial prophylaxis in 12-core transrectal prostate biopsy. Int J Urol. 2008;15(11):997-1001. accounted for. In summary, the analyzed evidence al- 22. Tuncel A, Aslan Y, Sezgin T, Aydin O, Tekdogan U, Atan A. Does dis- lows to conclude that, overall, there is therapeutic equiv- posable needle guide minimize infectious complications after transrectal prostate needle biopsy? Urology. 2008;71(6):1024-7; discussion 1027-8. alence of ciprofloxacin with the rest of antimicrobials 23. Peterson J, Kaul S, Khashab M, Fisher AC, Kahn JB. A double-blind, randomized comparison of levofloxacin 750 mg once-daily for five days used for the treatment of acute or complicated UTIs, with ciprofloxacin 400/500 mg twice-daily for 10 days for the treatment considering a similar capacity to that of other antimicro- of complicated urinary tract infections and acute pyelonephritis. Urology. 2008;71(1):17-22. bials to achieve bacteriological erradication and clinical 24. Dybowski B, JabÇonska O, Radziszewski P, Gromadzka-Ostrowska J, cure by the end of treatment and maintaining them in Borkowski A. Ciprofloxacin and furagin in acute cystitis: comparison of early immune and microbiological results. Int J Antimicrob Agents. subsequent stages, as well as a percentage of bacteri- 2008;31(2):130-4. 25. Peterson J, Kaul S, Khashab M, Fisher A, Kahn JB. Identification and al resistances similar to that of other antimicrobials. The pretherapy susceptibility of pathogens in patients with complicated uri- lower percentage of adverse events observed in the nary tract infection or acute pyelonephritis enrolled in a clinical study in the United States from November 2004 through April 2006. Clin Ther. ciprofloxacin group both in patients with acute (non-com- 2007;29(10):2215-21. 26. Klausner HA, Brown P, Peterson J, et al. A trial of levofloxacin 750 mg plicated) UTIs and in patients with risk factors, allows once daily for 5 days versus ciprofloxacin 400 mg and/or 500 mg twice continuing to recommend it as a superior alternative for daily for 10 days in the treatment of acute pyelonephritis. Curr Med Res Opin. 2007;23(11):2637-45. the management of these patients. 27. Marcelin-Jimenez G, Angeles AP, Martinez-Rossier L, Fernandez SA. Ciprofloxacin bioavailability is enhanced by oral co-administration with phenazopyridine: a pharmacokinetic study in a Mexican population. Clin References Drug Investig. 2006;26(6):323-8. 28. Esposito S, Noviello S, Leone S, et al. A pilot study on prevention of catheter-related urinary tract infections with fluoroquinolones. J Chemo- 1. Ronald AR, Nicolle LE, Stamm E, et al. Urinary tract infection in adults: ther. 2006;18(5):494-501. research priorities and strategies. Int J Antimicrob Agents. 2001;17(4): 29. Wagenlehner FM, Kinzig-Schippers M, Sorgel F, Weidner W, Naber KG. 343-8. Concentrations in plasma, urinary excretion and bactericidal activity of 2. Bacheller CD, Bernstein JM. Urinary tract infections. Med Clin North Am. levofloxacin (500 mg) versus ciprofloxacin (500 mg) in healthy volunteers 1997;81(3):719-30. receiving a single oral dose. Int J Antimicrob Agents. 2006;28(6):551-9. 3. Schappert SM. National Ambulatory Medical Care Survey: 1992 summa- 30. Mariappan P, Smith G, Moussa SA, Tolley DA. One week of ciprofloxacin ry. Adv Data. 1994;(253):1-20. before percutaneous nephrolithotomy significantly reduces upper tract 4. Kunin CM. Urinary tract infections in females. Clin Infect Dis. 1994;18(1):1-10. infection and urosepsis: a prospective controlled study. BJU Int. 5. Johnson JR, Stamm WE. Urinary tract infections in women: diagnosis 2006;98(5):1075-9. and treatment. Ann Intern Med. 1989;111(11):906-17. 31. Bin C, Hui W, Renyuan Z, et al. Outcome of cephalosporin treatment of 6. Albert X, Huertas I, Pereiro II, et al. Antibiotics for preventing recurrent bacteremia due to CTX-M-type extended-spectrum beta-lactamáse-pro- urinarytract infection in non-pregnant women. Cochrane Database Syst ducing Escherichia coli. Diagn Microbiol Infect Dis. 2006;56(4):351-7. Rev. 2004;(3):CD001209. 32. Kartal ED, Yenilmez A, Kiremitci A, Meric H, Kale M, Usluer G. Effective- 7. Milo G, Katchman EA, Paul M, et al. Duration of antibacterial treatment ness of ciprofloxacin prophylaxis in preventing bacteriuria caused by for uncomplicated urinary tract infection in women. Cochrane Database urodynamic study: a blind, randomized study of 192 patients. Urology. Syst Rev. 2005;(2):CD004682. 2006;67(6):1149-53. 226 P. Gutiérrez-Castrellón, et al.: Ciprofloxacin and urinary tract infections in adults
. 33 Wagenlehner FM, Kinzig-Schippers M, Tischmeyer U, et al. Pharmaco- 56. Naber KG, Theuretzbacher U, Moneva-Koucheva G, Stass H. Urinary kinetics of ciprofloxacin XR (1000 mg) versus levofloxacin (500 mg) in excretion and bactericidal activity of intravenous ciprofloxacin compared plasma and urine of male and female healthy volunteers receiving a with oral ciprofloxacin. Eur J Clin Microbiol Infect Dis. 1999;18(11):783-9. single oral dose. Int J Antimicrob Agents. 2006;27(1):7-14. 57. Price J, Ekleberry A, Grover A, et al. Evaluation of clinical practice 34. Gupta K, Hooton TM, Stamm WE. Isolation of fluoroquinolone-resistant guidelines on outcome of infection in patients in the surgical intensive rectal Escherichia coli after treatment of acute uncomplicated cystitis. J care unit. Crit Care Med. 1999;27(10):2118-24. Antimicrob Chemother. 2005;56(1):243-6. 58. Eickhoff JH, Frimodt-Miller N, Walter S, Frimodt-Miller C. A double-blind, 35. Carmignani G, De Rose AF, Olivieri L, Salvatori E, Rosignoli MT, Dionisio randomized, controlled multicentre study to compare the efficacy of P. Prulifloxacin versus ciprofloxacin in the treatment of adults with com- ciprofloxacin with pivampicillin as oral therapy for epididimytis in men plicated urinary tract infections. Urol Int. 2005;74(4):326-31. over 40 years of age. BJU Int. 1999;84(7):827-34. 36. Wazait HD, Patel HR, van der Meulen JH, et al. A pilot randomized 59. Henry DC, Nenad RC, Iravani A, et al. Comparison of sparfloxacin and double-blind placebo-controlled trial on the use of antibiotics on urinary ciprofloxacin in the treatment of community-acquired acute uncomplicat- catheter removal to reduce the rate of urinary tract infection: the pitfalls ed urinary tract infection in women. Sparfloxacin Multicenter Uncomplicat- of ciprofloxacin. BJU Int. 2004;94(7):1048-50. ed Urinary Tract Infection Study Group. Clin Ther. 1999;21(6): 966-81. 37. Dow G, Rao P, Harding G, et al. A prospective, randomized trial of 3 or 60. Tsukamoto T, Matsukawa M, Sano M, et al. Biofilm in complicated urinary 14 days of ciprofloxacin treatment for acute urinary tract infection in tract infection. Int J Antimicrob Agents. 1999;11(3-4):233-6; discussion 237-9. patients with spinal cord injury. Clin Infect Dis. 2004;39(5):658-64. 61. Iravani A, Klimberg I, Briefer C, Munera C, Kowalsky SF, Echols RM. A trial 38. Naber KG, Allin DM, Clarysse L, et al. Gatifloxacin 400 mg as a single comparing low-dose, short-course ciprofloxacin and standard 7 day therapy
shot or 200 mg once daily for 3 days is as effective as ciprofloxacin 250 with co-trimoxazole or nitrofurantoin in the treatment of uncomplicated urinary © Permanyer Publications 2015
.rehsilbup eht fo noissimrep nettirw roirp eht tuohtiw gniypocotohp ro decudorper eb yam noitacilbup siht fo trap oN trap fo siht noitacilbup yam eb decudorper ro mg twice dailygniypocotohp for the treatment oftuohtiw patients witheht uncomplicatedroirp urinary tractnettirw infection. J Antimicrob Chemother.noissimrep fo 1999;43 Suppleht A:67-75. .rehsilbup tract infections. Int J Antimicrob Agents. 2004;23(6):596-605. 62. McCarty JM, Richard G, Huck W, et al. A randomized trial of short-course 39. Sabbagh R, McCormack M, Piloquin F, et al. A prospective randomized ciprofloxacin, ofloxacin, or trimethoprim/sulfamethoxazole for the treat- trial of 1-day versus 3-day antibiotic prophylaxis for transrectal ultra- ment of acute urinary tract infection in women. Ciprofloxacin Urinary sound guided prostate biopsy. Can J Urol. 2004;11(2):2216-9. Tract Infection Group. Am J Med. 1999;106(3):292-9. 40. Wells WG, Woods GL, Jiang Q, Gesser RM. Treatment of complicated urinary 63. Mombelli G, Pezzoli R, Pinoja-Lutz G, Monotti R, Marone C, Franciolli M. tract infection in adults: combined analysis of two randomized, double-blind, Oral vs. intravenous ciprofloxacin in the initial empirical management of multicentre trials comparing ertapenem and ceftriaxone followed by appro- severe pyelonephritis or complicated urinary tract infections: a prospec- priate oral therapy. J Antimicrob Chemother. 2004;53 Suppl 2:ii67-74. tive randomized clinical trial. Arch Intern Med. 1999;159(1):53-8. 41. Valdevenito Sepúlveda JP. [Antibiotics in transurethral resection of the 64. Tsugawa M, Monden K, Nasu Y, Kumon H, Ohmori H. Prospective prostate in patients with low risk of infectious complications: randomized randomized comparative study of antibiotic prophylaxis in urethrocys- prospective comparative study]. Arch Esp Urol. 2004;57(1):48-57. toscopy and urethrocystography. Int J Urol. 1998;5(5):441-3. 42. Naber KG, Bartnicki A, Bischoff W, et al. Gatifloxacin 200 mg or 400 mg 65. Kapoor DA, Klimberg IW, Malek GH, et al. Single-dose oral ciprofloxacin once daily is as effective as ciprofloxacin 500 mg twice daily for the versus placebo for prophylaxis during transrectal prostate biopsy. Urol- treatment of patients with acute pyelonephritis or complicated urinary ogy. 1998;52(4):552-8. tract infections. Int J Antimicrob Agents. 2004;23 Suppl 1:S41-53. 66. Naber KG, Theuretzbacher U, Kinzig M, Savov O, Sorgel F. Urinary 43. Vogel T, Verreault R, Gourdeau M, Morin M, Grenier-Gosselin L, Rochette excretion and bactericidal activities of a single oral dose of 400 milli- L. Optimal duration of antibiotic therapy for uncomplicated urinary tract grams of fleroxacin versus a single oral dose of 800 milligrams of pe- infection in older women: a double-blind randomized controlled trial. floxacin in healthy volunteers. Antimicrob Agents Chemother. CMAJ. 2004;170(4):469-73. 1998;42(7):1659-65. 44. Talan DA, Klimberg IW, Nicolle LE, Song J, Kowalsky SF, Church DA. Once 67. Hsieh WJ, Lin HC, Hwang SJ, et al. The effect of ciprofloxacin in the daily, extended release ciprofloxacin for complicated urinary tract infections prevention of bacterial infection in patients with cirrhosis after upper and acute uncomplicated pyelonephritis. J Urol. 2004;171(2 Pt 1):734-9. gastrointestinal bleeding. Am J Gastroenterol. 1998;93(6):962-6. 45. Wagenlehner FM, Wydra S, Onda H, Kinzig-Schippers M, Sorgel F, 68. Viitanen J, Malminiemi K, Kallio J, Puolakka VM, Rajala P, Tammela TL. Naber KG. Concentrations in plasma, urinary excretion, and bactericid- Transurethral prostatectomy in patients with preoperative bacteriuria: al activity of linezolid (600 milligrams) versus those of ciprofloxacin (500 double-blind study with oral fleroxacin and cefalexin. Chemotherapy. milligrams) in healthy volunteers receiving a single oral dose. Antimicrob 1998;44(1):69-75. Agents Chemother. 2003;47(12):3789-94. 69. Moyses Neto M, Costa RS, Reis MA, et al. Use of ciprofloxacin as a 46. Ulleryd P, Sandberg T. Ciprofloxacin for 2 or 4 weeks in the treatment prophylactic agent in urinary tract infections in renal transplant recipi- of febrile urinary tract infection in men: a randomized trial with a 1 year ents. Clin Transplant. 1997;11(5 Pt 1):446-52. follow-up. Scand J Infect Dis. 2003;35(1):34-9. 70. Frankenschmidt A, Naber KG, Bischoff W, Kullmann K. Once-daily flerox- 47. Henry DC Jr, Bettis RB, Riffer E, et al. Comparison of once-daily extend- acin versus twice-daily ciprofloxacin in the treatment of complicated ed-release ciprofloxacin and conventional twice-daily ciprofloxacin for urinary tract infections. J Urol. 1997;158(4):1494-9. the treatment of uncomplicated urinary tract infection in women. Clin 71. Rao VV, Rambhau D, Rao BR, Srinivasu P. Circadian variation in urinary Ther. 2002;24(12):2088-104. excretion of ciprofloxacin after a single-dose oral administration at 1000 48. Naber KG; European Lomefloxacin Prostatitis Study Group. Lomefloxa- and 2200 hours in human subjects. Antimicrob Agents Chemother. cin versus ciprofloxacin in the treatment of chronic bacterial prostatitis. 1997;41(8):1802-4. Int J Antimicrob Agents. 2002;20(1):18-27. 72. Lukkarinen O, Hellstrom P, Leppilahti M, Kontturi M, Tammela T. Antibi- 49. Cox CE, Marbury TC, Pittman WG, et al. A randomized, double-blind, otic prophylaxis in patients with urinary retention undergoing transure- multicenter comparison of gatifloxacin versus ciprofloxacin in the treat- thral prostatectomy. Ann Chir Gynaecol. 1997;86(3):239-42. ment of complicated urinary tract infection and pyelonephritis. Clin Ther. 73. Bierkens AF, Hendrikx AJ, Ezz el Din KE, et al. The value of antibiotic 2002;24(2):223-36. prophylaxis during extracorporeal shock wave lithotripsy in the preven- 50. Auquer F, Cordinn F, Gorina E, et al. Single-dose ciprofloxacin versus 3 tion of urinary tract infections in patients with urine proven sterile prior days of norfloxacin in uncomplicated urinary tract infections in women. to treatment. Eur Urol. 1997;31(1):30-5. Clin Microbiol Infect. 2002;8(1):50-4. 74. Whitby M, Angus L, Nimmo G, Hill V. Complicated urinary infection in 51. Richard GA, Mathew CP, Kirstein JM, Orchard D, Yang JY. Single-dose flu- spinal injury patients: fleroxacin compared with ciprofloxacin. Chemo- oroquinolone therapy of acute uncomplicated urinary tract infection in women: therapy. 1996;42(6):468-72. results from a randomized, double-blind, multicenter trial comparing sin- 75. Gasser TC, Wisard M, Frei R. Oral fleroxacin prophylaxis in transurethral gle-dose to 3-day fluoroquinolone regimens. Urology. 2002;59(3):334-9. surgery. J Urol. 1996;156(1):146-8. 52. Gomolin IH, Siami PF, Reuning-Scherer J, Haverstock DC, Heyd A; Oral 76. Pisani E, Bartoletti R, Trinchieri A, Rizzo M. Lomefloxacin versus cipro- Suspension Study Group. Efficacy and safety of ciprofloxacin oral sus- floxacin in the treatment of complicated urinary tract infections: a multi- pension versus trimethoprim-sulfamethoxazole oral suspension for treat- center study. J Chemother. 1996;8(3):210-3. ment of older women with acute urinary tract infection. J Am Geriatr Soc. 77. Hall JC, Christiansen KJ, England P, et al. Antibiotic prophylaxis for 2001;49(12):1606-13. patients undergoing transurethral resection of the prostate. Urology. 53. Raz R, Naber KG, Raizenberg C, et al. Ciprofloxacin 250 mg twice daily 1996;47(6):852-6. versus ofloxacin 200 mg twice daily in the treatment of complicated urinary 78. Naber KG, di Silverio F, Geddes A, Guibert J. Comparative efficacy of tract infections in women. Eur J Clin Microbiol Infect Dis. 2000;19(5):327-31. sparfloxacin versus ciprofloxacin in the treatment of complicated urinary 54. Aron M, Rajeev TP, Gupta NP. Antibiotic prophylaxis for transrectal tract infection. J Antimicrob Chemother. 1996;37 Suppl A:135-44. needle biopsy of the prostate: a randomized controlled study. BJU Int. 79. Lukkarinen O, Hellstrom P, Leppilahti M, Kontturi M, Tammela T. Prospec- 2000;85(6):682-5. tive randomized open study between ciprofloxacin and a combination of 55. Christiano AP, Hollowell CM, Kim H, et al. Double-blind randomized sulfadiazine and trimethoprim in antibiotic prophylaxis in connection with comparison of single-dose ciprofloxacin versus intravenous cefazolin in transurethral prostatectomy. Scand J Urol Nephrol. 1996; 30(1):33-6. patients undergoing outpatient endourologic surgery. Urology. 2000; 80. Iravani A, Tice AD, McCarty J, et al. Short-course ciprofloxacin treatment 55(2):182-5. of acute uncomplicated urinary tract infection in women. The minimum 227 Gaceta Médica de México. 2015;151
effective dose. The Urinary Tract Infection Study Group [corrected]. Arch 107. Karachalios GN, Georgiopoulos AN, Nasopoulou-Papadimitriou DD, Intern Med. 1995;155(5):485-94. Adracta DJ. Value of single-dose ciprofloxacin in the treatment of acute 81. McCue JD, Gaziano P, Orders D. A randomised controlled trial of oflox- uncomplicated urinary tract infection in women. Drugs Exp Clin Res. acin 200 mg 4 times daily or twice daily vs ciprofloxacin 500 mg twice 1991;17(10-11):521-4. daily in elderly nursing home patients with complicated UTI. Drugs. 108. Brouwer WK, Hoogkamp-Korstanje JA, Kuiper KM. Antibiotic prophylax- 1995;49 Suppl 2:368-73. is in vaginal hysterectomy. Three doses of cefuroxime plus metronida- 82. Darouiche RO, Smith MS, Markowski J. Antibiotic prophylaxis for urody- zole versus one dose of ciprofloxacin. Pharm Weekbl Sci. namic testing in patients with spinal cord injury: a preliminary study. J 1990;12(6A):292-4; discussion 294-5. Hosp Infect. 1994;28(1):57-61. 109. Boyko EJ, Iravani A, Silverman MH, Schelling DJ, Wright RA. Random- 83. Pfau A, Sacks TG. Effective postcoital quinolone prophylaxis of recurrent ized, controlled trial of a 10-day course of amifloxacin versus trimetho- urinary tract infections in women. J Urol. 1994;152(1):136-8. prim-sulfamethoxazole in the treatment of acute, uncomplicated urinary 84. Biering-Sorensen F, Hiiby N, Nordenbo A, Ravnborg M, Bruun B, Rahm tract infection. Amifloxacin Multi-Center Trial Group. Antimicrob Agents V. Ciprofloxacin as prophylaxis for urinary tract infection: prospective, Chemother. 1990;34(4):665-7. randomized, cross-over, placebo controlled study in patients with spinal 110. Wolfhagen MJ, Hoepelman AI, Verhoef J. Double-blind, dose-range-finding cord lesion. J Urol. 1994;151(1):105-8. Erratum in: J Urol. 1994;151(4):1032. study of fleroxacin (RO 23-6240; AM-833) for treatment of complicated 85. Whitby M, Brown P, Silagy C, Rana C. Comparison of fleroxacin and urinary tract infections. Antimicrob Agents Chemother. 1990;34(3):409-12. amoxicillin in the treatment of uncomplicated urinary tract infections in 111. Van Poppel H, Willemen P, Wegge M, Kraseman P, Chysky V, Baert L. women. Am J Med. 1993;94(3A):97S-100S. Antibiotic cover of transurethral maneuvers with ciprofloxacin and sus-
86. Iravani A. Multicenter study of single-dose and multiple-dose fleroxacin ceptibility behavior of pathogens in patients with neurogenic bladder. © Permanyer Publications 2015
.rehsilbup eht fo noissimrep nettirw roirp eht tuohtiw gniypocotohp ro decudorper eb yam noitacilbup siht fo trap oN trap fo siht noitacilbup yam eb decudorper ro versus ciprofloxacingniypocotohp in the treatmenttuohtiw of uncomplicatedeht urinaryroirp tract in- Unettirw rol Int. 1990;45(6):342-5. noissimrep fo eht .rehsilbup fections. Am J Med. 1993;94(3A):89S-96S. 112. Raz R, Rottensterich E, Hefter H, Kennes Y, Potasman I. Single-dose 87. Cox CE. Comparison of intravenous fleroxacin with ceftazidime for treat- ciprofloxacin in the treatment of uncomplicated urinary tract infection in ment of complicated urinary tract infections. Am J Med. 1993;94(3A): women. Eur J Clin Microbiol Infect Dis. 1989;8(12):1040-2. 118S-125S. 113. Cox CE. Comparison of intravenous ciprofloxacin and intravenous cefo- 88. Naber KG, Sigl G. Fleroxacin versus ofloxacin in patients with compli- taxime for antimicrobial prophylaxis in transurethral surgery. Am J Med. cated urinary tract infection: a controlled clinical study. Am J Med. 1989;87(5A):252S-254S. 1993;94(3A):114S-117S. 114. Sifuentes-Osornio J, Macas A, Amieva RI, Ramos A, Ruiz-Palacios GM. 89. Pummer K. Fleroxacin versus norfloxacin in the treatment of urinary tract Intravenous ciprofloxacin and ceftazidime in serious infections. A pro- infections: a multicenter, double-blind, prospective, randomized, com- spective, controlled clinical trial with third-party blinding. Am J Med. parative study. Am J Med. 1993;94(3A):108S-113S. 1989;87(5A):202S-205S. 90. Childs SJ. Fleroxacin versus norfloxacin for oral treatment of serious 115. Quintero-Perez NP, Andrade-Villaneuva JF, Leon-Garnica G, Bertin-Mon- urinary tract infections. Am J Med. 1993;94(3A):105S-107S. tano M, Rodriguez-Chagollan JJ, Rodriguez-Noriega E. Efficacy and 91. Pittman W, Moon JO, Hamrick LC Jr, et al. Randomized double-blind safety of intravenous ciprofloxacin in the treatment of serious infections. trial of high- and low-dose fleroxacin versus norfloxacin for complicated A comparison with ceftazidime. Am J Med. 1989;87(5A):198S-201S. urinary tract infection. Am J Med. 1993;94(3A):101S-104S. 116. Villavicencio J, Asensio de Fernandez ME, Ramirez CA. Intravenous 92. Pfau A, Sacks TG. Single dose quinolone treatment in acute uncompli- ciprofloxacin or ceftazidime in selected infections. A prospective, ran- cated urinary tract infection in women. J Urol. 1993;149(3):532-4. domized, controlled study. Am J Med. 1989;87(5A):191S-194S. 93. Grubbs NC, Schultz HJ, Henry NK, Ilstrup DM, Muller SM, Wilson WR. 117. Peacock JE Jr, Pegram PS, Weber SF, Leone PA. Prospective, random- Ciprofloxacin versus trimethoprim-sulfamethoxazole: treatment of com- ized comparison of sequential intravenous followed by oral ciprofloxacin munity-acquired urinary tract infections in a prospective, controlled, with intravenous ceftazidime in the treatment of serious infections. Am J double-blind comparison. Mayo Clin Proc. 1992;67(12):1163-8. Med. 1989;87(5A):185S-190S. 94. Schaeffer AJ, Anderson RU. Efficacy and tolerability of norfloxacin vs. 118. Gallis HA, Brennan RO, Goodwin SD, Swinney V, Rumbaugh MM, Drew ciprofloxacin in complicated urinary tract infection. Urology. 1992; RH. Comparison of the safety and efficacy of intravenous ciprofloxacin 40(5):446-9. and intravenous ceftazidime in the treatment of selected infections. Am 95. Hibberd PL, Tolkoff-Rubin NE, Doran M, et al. Trimethoprim-sulfamethoxaz- J Med. 1989;87(5A):176S-180S. ole compared with ciprofloxacin for the prevention of urinary tract infection 119. Levine DP, McNeil P, Lerner SA. Randomized, double-blind comparative in renal transplant recipients. A double-blind, randomized controlled trial. study of intravenous ciprofloxacin versus ceftazidime in the treatment of Online J Curr Clin Trials. 1992;Doc No 15:[4083 words; 46 paragraphs]. serious infections. Am J Med. 1989;87(5A):160S-163S. 96. Peters HJ. Sequential therapy with ofloxacin in complicated urinary tract 120. Fass RJ, Plouffe JF, Russell JA. Intravenous/oral ciprofloxacin versus infections: a randomized comparative study with ciprofloxacin. Infection. ceftazidime in the treatment of serious infections. Am J Med. 1989; 1992;20(3):172-3. 87(5A):164S-168S. 97. Van der Wall E, Verkooyen RP, Mintjes-de Groot J, et al. Prophylactic 121. Abbas AM, Chandra V, Dongaonkar PP, et al. Ciprofloxacin versus ciprofloxacin for catheter-associated urinary-tract infection. Lancet. amoxycillin/clavulanic acid in the treatment of urinary tract infections in 1992;339(8799):946-51. general practice. J Antimicrob Chemother. 1989;24(2):235-9. 98. Cox CE. A comparison of the safety and efficacy of lomefloxacin and 122. Shearman CP, Silverman SH, Johnson M, et al. Single dose, oral antibi- ciprofloxacin in the treatment of complicated or recurrent urinary tract otic cover for transurethral prostatectomy. Br J Urol. 1988;62(5): 434-8. infections. Am J Med. 1992;92(4A):82S-86S. 123. Kosmidis J, Gargalianos P, Adamis G, Petropoulou D, Makris D. Flerox- 99. Bailey RR, Lynn KL, Robson RA, Peddie BA, Smith A. Comparison of acin in single dose oral therapy of uncomplicated lower urinary tract ciprofloxacin with netilmicin for the treatment of acute pyelonephritis. N infection. J Antimicrob Chemother. 1988;22 Suppl D:219-21. Z Med J. 1992;105(930):102-3. 124. Polubiec A, Weuta H, Stepka K, Ktos K, Strazynska R, Jorasz J. Bacte- 100. Stein GE, Philip E. Comparison of three-day temafloxacin with seven-day rial infections of the lower urinary tract treated with ciprofloxacin or ce- ciprofloxacin treatment of urinary tract infections in women. J Fam Pract. falexin--a comparative study. Infection. 1988;16 Suppl 1:S62-4. 1992;34(2):180-4. 125. Goldstein EJ, Kahn RM, Alpert ML, Ginsberg BP, Greenway FL, Citron 101. Kalager T, Andersen BM, Bergan T, et al. Ciprofloxacin versus a tobra- DM. Ciprofloxacin versus cinoxacin in therapy of urinary tract infections. mycin/cefuroxime combination in the treatment of serious systemic in- A randomized, double-blind trial. Am J Med. 1987;82(4A):284-7. fections: a prospective, randomized and controlled study of efficacy and 126. Garlando F, Rietiker S, Tiuber MG, Flepp M, Meier B, Lothy R. Single-dose safety. Scand J Infect Dis. 1992;24(5):637-46. Erratum in: Scand J Infect ciprofloxacin at 100 versus 250 mg for treatment of uncomplicated urinary Dis. 1993;25(2):271. tract infections in women. Antimicrob Agents Chemother. 1987;31(2):354-6. 102. Iravani A. Treatment of uncomplicated urinary tract infections with 127. Henry NK, Schultz HJ, Grubbs NC, Muller SM, Ilstrup DM, Wilson WR. temafloxacin. Am J Med. 1991;91(6A):124S-128S. Comparison of ciprofloxacin and co-trimoxazole in the treatment of un- 103. Paladino JA, Sperry HE, Backes JM, et al. Clinical and economic eval- complicated urinary tract infection in women. J Antimicrob Chemother. uation of oral ciprofloxacin after an abbreviated course of intravenous 1986;18 Suppl D:103-6. antibiotics. Am J Med. 1991;91(5):462-70. 128. Gonzalez MA, Moranchel AH, Duran S, et al. Multiple-dose pharmaco- 104. Fang GD, Brennen C, Wagener M, et al. Use of ciprofloxacin versus use kinetics of ciprofloxacin administered intravenously to normal volunteers. of aminoglycosides for therapy of complicated urinary tract infection: Antimicrob Agents Chemother. 1985;28(2):235-9. prospective, randomized clinical and pharmacokinetic study. Antimicrob 129. Giamarellou H, Efstratiou A, Tsagarakis J, Petrikkos G, Daikos GK. Ex- Agents Chemother. 1991;35(9):1849-55. perience with ciprofloxacin in vitro and in vivo. Arzneimittelforschung. 105. Lew MA, Kehoe K, Ritz J, et al. Prophylaxis of bacterial infections with 1984;34(12):1775-8. ciprofloxacin in patients undergoing bone marrow transplantation. Trans- 130. Dickersin K, Scherer R, Lefebvre C. Identifying relevant studies for plantation. 1991;51(3):630-6. systematic reviews. BMJ. 1994;309(6964):1286-91. 106. Rapp RP, Billeter M, Hatton J, Young AB, Tibbs PA, Dempsey RJ. Intra- 131. Lefebvre C, McDonald S. Development of a sensitive search strategy for venous ciprofloxacin versus ceftazidime for treatment of nosocomial reports of randomized controlled trials in EMBASE. Fourth International pneumonia and urinary tract infection. Clin Pharm. 1991;10(1):49-55. Cochrane Colloquium; 1996 Oct 20-24; Adelaide (Australia). 228